Dr. Gary Steinberg: How to Improve Brain Health & Offset Neurodegeneration

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.260 | where we discuss science

00:00:03.660 | and science-based tools for everyday life.

00:00:05.900 | I'm Andrew Huberman,

00:00:10.280 | and I'm a professor of neurobiology and ophthalmology

00:00:13.340 | at Stanford School of Medicine.

00:00:15.140 | My guest today is Dr. Gary Steinberg.

00:00:17.620 | Dr. Gary Steinberg is a medical doctor,

00:00:19.740 | PhD professor of neurosurgery, neurosciences,

00:00:22.820 | and neurology at Stanford University School of Medicine.

00:00:26.340 | He is a world expert

00:00:27.400 | in what is called the cerebrovascular architecture

00:00:29.780 | of our brain,

00:00:30.900 | which is a scientific term explaining how blood flow

00:00:33.620 | to the brain supplies oxygen and critical nutrients

00:00:36.260 | to our neurons, our nerve cells,

00:00:38.060 | as well as playing a critical role

00:00:39.400 | in removing waste products from our brain

00:00:41.580 | in order for our brain to function normally.

00:00:44.160 | During today's discussion,

00:00:45.180 | he explains in very clear terms

00:00:47.140 | how blood flow to the brain occurs

00:00:49.220 | and how disruptions in blood flow,

00:00:50.960 | in things like stroke and aneurysm,

00:00:53.340 | impact brain functioning.

00:00:54.900 | We also discuss concussions and TBI,

00:00:57.500 | or traumatic brain injuries,

00:00:58.800 | which unfortunately are very common

00:01:00.500 | and what can be done to treat concussion

00:01:02.780 | and traumatic brain injury.

00:01:04.300 | Dr. Steinberg also shares with us recent findings

00:01:06.740 | from his laboratory and clinic,

00:01:08.700 | revealing how stem cells can be used

00:01:10.680 | to recover function in the human brain and spinal cord

00:01:13.680 | after things like concussion, TBI, stroke,

00:01:16.820 | and other disruptions to the cerebrovascular architecture.

00:01:19.980 | And he shares with us the science supported tools,

00:01:22.020 | that is protocols, that any of us can use

00:01:24.540 | to improve the health and functioning of our brains.

00:01:27.420 | So if you or somebody that you know

00:01:28.900 | has experienced concussion or traumatic brain injury,

00:01:31.300 | stroke, or aneurysm,

00:01:32.860 | today's discussion is sure to include

00:01:34.980 | vital information for you.

00:01:36.380 | And for those fortunate enough

00:01:37.540 | to not have experienced those conditions,

00:01:39.460 | today's discussion will also review

00:01:41.360 | the latest science and protocols

00:01:43.260 | for improving brain health.

00:01:44.820 | Before we begin, I'd like to emphasize

00:01:46.620 | that this podcast is separate

00:01:48.140 | from my teaching and research roles at Stanford.

00:01:50.240 | It is, however, part of my desire and effort

00:01:52.240 | to bring zero cost to consumer information

00:01:54.080 | about science and science-related tools

00:01:56.020 | to the general public.

00:01:57.380 | In keeping with that theme,

00:01:58.420 | I'd like to thank the sponsors of today's podcast.

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00:04:48.200 | Aeropress is like a French press,

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00:05:54.000 | I usually mention this at the end of episodes,

00:05:55.820 | but if you're learning from

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00:06:12.560 | And now for my discussion with Dr. Gary Steinberg.

00:06:16.420 | Dr. Gary Steinberg, welcome.

00:06:18.760 | - Thank you, Andrew, pleasure to be here.

00:06:21.160 | - I have a lot of questions.

00:06:22.400 | I know people are interested in keeping their brains healthy

00:06:25.320 | and sadly, things happen to the brain,

00:06:28.960 | sometimes as a consequence of aging,

00:06:31.160 | sometimes as a consequence of certain activities.

00:06:34.000 | Maybe you could just explain for us right off the bat,

00:06:37.280 | what is a stroke?

00:06:38.560 | What is an aneurysm?

00:06:40.280 | What is a hemorrhage?

00:06:41.640 | Where do these terms overlap?

00:06:43.000 | How are they different?

00:06:44.160 | Obviously, none of us want these things.

00:06:46.920 | And we will talk about ways to prevent them

00:06:50.060 | and your ways of treating them as well, of course.

00:06:52.740 | But just to start off,

00:06:53.820 | maybe we can just lay down the nomenclature.

00:06:56.000 | - Sure, so a stroke is like a heart attack of the brain.

00:07:00.480 | It involves disruption of blood flow to the brain,

00:07:03.400 | either in the form of a blocked vessel

00:07:06.360 | or less likely a hemorrhage.

00:07:08.240 | About 87% of strokes are due to a clot,

00:07:15.160 | either forming in the brain artery itself

00:07:18.280 | or forming closer to the heart,

00:07:20.920 | in the heart or in the carotid artery

00:07:22.680 | and dislodging and blocking blood flow to the brain.

00:07:26.440 | About 13% are caused by a hemorrhage,

00:07:29.320 | bursting of a blood vessel.

00:07:31.480 | And that results in lack of oxygen and glucose

00:07:35.560 | being delivered to the brain cells.

00:07:38.000 | And that ultimately causes death of tissue

00:07:41.200 | and disruption of bodily functions, neurologic function.

00:07:44.720 | That's what a stroke is.

00:07:46.660 | - How do we know if we have clots residing in our body

00:07:49.600 | that could be dislodged?

00:07:51.200 | I know that some people when they fly wear compression socks.

00:07:55.780 | I know that some people have genetic mutations

00:08:00.640 | that affect clotting.

00:08:02.080 | I'll raise my hand here and I'll do a disclosure.

00:08:05.160 | I did some genetic testing.

00:08:06.840 | I'm a heterozygote for factor V Leiden,

00:08:10.800 | which is a clotting factor.

00:08:13.280 | Heterozygote folks means I have one mutant copy.

00:08:16.360 | So fortunately I don't suffer from excessive bleeding

00:08:20.560 | or clotting, but there are lifestyle factors

00:08:23.460 | that can exacerbate an existing mutation like that.

00:08:27.840 | People who are homozygous mutants for factor V Leiden,

00:08:30.080 | of course, at much greater risk for clotting and bleeding.

00:08:34.200 | So I just disclosed a lot.

00:08:38.040 | Maybe you could comment on some of the clotting factors

00:08:40.560 | and lifestyle factors that impact clotting,

00:08:42.880 | but how would somebody know if they've got a clot

00:08:45.480 | that could potentially go to their brain?

00:08:46.840 | - Sure, well, you might not know.

00:08:48.520 | In many cases you don't know, and that's the problem.

00:08:51.840 | You can have a predisposition, as you say,

00:08:55.120 | due to certain genes that are mutated or represented

00:09:00.120 | that predispose to clots.

00:09:05.160 | And those clots can occur on the arterial side

00:09:08.240 | or the venous side.

00:09:10.200 | The arterial side is what generally causes a stroke,

00:09:14.640 | an ischemic stroke.

00:09:16.360 | On the venous side, you can sometimes have problems.

00:09:21.000 | When you talk about flying, not moving your legs,

00:09:24.480 | developing clots in your legs, wearing compression boots,

00:09:27.440 | that's on the venous side, and that can cause something

00:09:31.560 | like a deep vein thrombosis, which is not good

00:09:36.000 | 'cause it can travel to the lung

00:09:38.040 | and cause a pulmonary embolus.

00:09:40.200 | That generally on the venous side does not go to the brain.

00:09:43.680 | - Oh, good, in my case, that feels fortunate, yeah.

00:09:46.160 | - Exactly, you can develop some venous problems

00:09:49.280 | in the brain, which can cause a venous-type stroke.

00:09:53.040 | That's much less common, and the way that causes a stroke

00:09:56.360 | is not lack of blood flow being delivered to the brain,

00:10:00.000 | but by having a clot in an important vein,

00:10:03.960 | the blood can't get out of the brain.

00:10:06.000 | It backs up and causes swelling or edema,

00:10:09.760 | but that's much less common.

00:10:12.560 | Generally, we talk about strokes as being arterial

00:10:16.360 | in nature and either blockage of a blood vessel

00:10:21.360 | or bursting of a vessel.

00:10:24.240 | - What are some things that impact clotting

00:10:27.680 | and/or excessive bleeding?

00:10:30.560 | My understanding is these factor V Leiden mutations

00:10:33.520 | are one example.

00:10:35.080 | The other is, let's say somebody takes,

00:10:37.720 | say, a blood-thinning agent like baby aspirin,

00:10:42.060 | or I'm told, and I'll have to check this,

00:10:46.400 | I'm sure people will say in the YouTube comments,

00:10:48.040 | that if you take lots and lots of, say, fish oil

00:10:50.940 | or things like that, you can become more of a bleeder.

00:10:53.120 | Some people out there are hemophiliacs,

00:10:55.720 | and then my understanding is also that certain forms

00:10:58.380 | of oral contraception for women

00:10:59.960 | can increase the rates of bleeding.

00:11:03.160 | So tell me if I'm wrong about any of those

00:11:05.640 | and if any of those things predispose people

00:11:08.700 | to more stroke or hemorrhage.

00:11:11.600 | - Sure, so different kinds of drugs thin the blood,

00:11:16.600 | and they can predispose you to having a larger hemorrhage

00:11:22.280 | than you would if something bursts,

00:11:26.600 | or if you fall and have some traumatic injury to your brain

00:11:31.840 | or anywhere in the body.

00:11:33.800 | In general, they don't cause a hemorrhage

00:11:36.960 | because they're fairly safe,

00:11:38.520 | but if there's, as I say, some interruption to the body,

00:11:43.520 | like a bruise, it would be a much worse type of bleed.

00:11:50.840 | So aspirin is a type of antiplatelet agent

00:11:55.040 | that thins the blood.

00:11:56.040 | There are many types of antiplatelet agents,

00:11:58.060 | and they're very, very useful for treating people

00:12:01.940 | who have a predisposition to develop clots

00:12:05.660 | 'cause they thin the blood.

00:12:07.340 | Anticoagulants are another type.

00:12:09.520 | They're known as Coumadin, Warfarin, Eliquis.

00:12:14.820 | There's lots of new agents,

00:12:17.380 | and they're often taken orally

00:12:20.440 | or can be given intravenously.

00:12:22.740 | Heparin's another one.

00:12:24.580 | Again, they thin the blood,

00:12:26.980 | so they would put someone

00:12:29.580 | at somewhat increased risk for hemorrhage.

00:12:32.180 | Then, as far as oral contraceptives,

00:12:37.100 | if you go back to the 1970s

00:12:39.500 | when the oral contraceptives first generation

00:12:43.100 | were coming out, it turns out,

00:12:45.860 | and they were heavily estrogen-dominated

00:12:49.580 | rather than progesterone.

00:12:52.220 | They did, and they still, to some extent,

00:12:54.540 | increased the risk of developing clots.

00:12:57.100 | So women back in the '70s

00:12:59.620 | who took oral contraceptives and smoked

00:13:03.380 | had a very, very high incidence

00:13:06.180 | of developing clots and ischemic strokes

00:13:09.900 | and clots elsewhere in the body.

00:13:12.060 | The newer generations are much safer

00:13:15.800 | in terms of developing clots,

00:13:17.740 | but for my patients,

00:13:20.260 | many of whom have had strokes

00:13:21.860 | or are at risk for stroke,

00:13:23.300 | we recommend that the women

00:13:25.180 | do not take oral contraceptives,

00:13:28.140 | that they use some other form.

00:13:29.780 | IUD, for instance, may have a little bit

00:13:32.800 | of progesterone, which is released locally,

00:13:35.580 | but it doesn't cause a large increase

00:13:38.340 | in estrogens or progesterone systemically.

00:13:42.300 | So we still believe that the oral contraceptives

00:13:46.000 | increased the risk somewhat,

00:13:47.400 | not the way it did for first generation.

00:13:50.480 | And then there are other modifiable factors

00:13:52.920 | besides the genetic ones.

00:13:54.880 | So smoking is a very high risk factor

00:13:58.960 | for developing clots,

00:14:00.920 | which can lead to strokes, heart attacks,

00:14:05.760 | peripheral vascular disease.

00:14:07.500 | High lipids is another.

00:14:12.160 | So when people have high, bad cholesterol, LDL,

00:14:17.160 | it's recommended that if they can't reduce it with diet,

00:14:22.160 | that they take a statin.

00:14:25.240 | The statins are very, very effective

00:14:27.720 | in lowering the bad cholesterol,

00:14:29.400 | preventing strokes and heart attack.

00:14:31.080 | Interestingly, the statins have also been shown

00:14:34.160 | to be highly beneficial for the blood vessel integrity,

00:14:38.140 | even if you don't have high LDL.

00:14:40.520 | - Interesting.

00:14:41.340 | - So they have other beneficial properties.

00:14:42.560 | So again, for my patients,

00:14:44.480 | I often recommend they take a statin,

00:14:47.520 | even if they don't have high cholesterol.

00:14:50.480 | - Interesting.

00:14:51.320 | - And then hypertension is another risk factor

00:14:54.600 | for developing clots and arterial disease.

00:14:59.040 | - When you say that smoking dramatically increases

00:15:01.040 | the risk of stroke, is that because of nicotine per se?

00:15:04.520 | Is it the vasoconstriction and blood pressure elevation

00:15:08.080 | that comes from nicotine itself?

00:15:09.440 | Or is there something about smoking,

00:15:11.520 | maybe even vaping, I don't know,

00:15:13.840 | that the contaminants, the other chemicals,

00:15:17.360 | in cigarettes or vape chemicals,

00:15:20.640 | that increases the stroke risk?

00:15:22.840 | Or is it nicotine itself?

00:15:24.320 | - It's not just nicotine.

00:15:25.640 | Nicotine is one of the factors,

00:15:27.260 | but it's the other products that are produced by smoking

00:15:31.960 | that can have an effect.

00:15:33.560 | - So given that so many fewer, at least Americans,

00:15:36.340 | and I think worldwide, people are smoking less,

00:15:39.800 | are we seeing less stroke?

00:15:42.240 | - Yes, the incidence of stroke is actually decreasing.

00:15:45.300 | It may be in part due to decreased smoking,

00:15:49.560 | but it also is in part due to other modifiable factors.

00:15:53.880 | So hypertension is much better treated now

00:15:58.200 | than it used to be.

00:15:59.560 | People take better care of themselves

00:16:01.320 | in terms of other lifestyle factors.

00:16:04.040 | So people exercise more.

00:16:07.480 | There's a lower incidence in some subgroups of obesity.

00:16:12.480 | Those are the risk factors also for developing strokes

00:16:16.400 | and as well as heart attack.

00:16:18.140 | - What is the relationship between heart health

00:16:22.680 | and brain health as it relates to stroke?

00:16:24.880 | I would imagine that anything that's good for our heart

00:16:27.600 | is probably good for our brain,

00:16:29.840 | given the enormous amounts of blood and glucose

00:16:34.720 | that the brain requires to function normally.

00:16:37.840 | - Yeah, it's a good point.

00:16:39.800 | In general, the things that are good for the heart

00:16:44.120 | are good for the brain.

00:16:45.280 | There are differences between the heart and the brain,

00:16:47.480 | but they both depend very much on blood flow.

00:16:52.480 | The brain's unique, though,

00:16:53.560 | because the brain represents only 2% of the body weight,

00:16:58.560 | yet it draws 15% of the total blood flow

00:17:04.720 | and remarkably, it consumes 20% of the body's oxygen.

00:17:09.720 | - Amazing. - So the brain,

00:17:11.040 | I still think the brain is the most important organ,

00:17:14.160 | not the heart, not the kidneys, but I'm biased, of course.

00:17:17.920 | - Yeah, you've spent some time

00:17:18.920 | in the landscape of the brain.

00:17:21.840 | Yeah, it's clear that of all the tissues in the body,

00:17:26.640 | if you had to pick one tissue to remove one cubic millimeter

00:17:31.940 | of that tissue, that your brain,

00:17:33.420 | and probably the neural retina

00:17:34.460 | would be your least favorite choice,

00:17:38.060 | just given the deficits that can result.

00:17:40.040 | - Right, and of course, the brain also is what makes us human.

00:17:43.700 | - Right, speaking of which,

00:17:44.980 | if we take a little departure into neurosurgery itself,

00:17:48.740 | your specialty, of all the years of doing brain surgery,

00:17:53.740 | can you recall maybe one of the most incredible moments

00:18:01.700 | or days that allowed for some insight

00:18:04.380 | into how the brain works by virtue of, let's say,

00:18:07.800 | stimulating a given brain area

00:18:09.460 | or removing a given brain area or something of that sort?

00:18:13.140 | I ask this because so very few of us

00:18:15.980 | will ever have the opportunity to do what you do,

00:18:18.300 | and if I were here talking to an astronaut,

00:18:20.380 | and by the way, I consider neurosurgeons

00:18:21.820 | the astronauts of neuroscience,

00:18:23.660 | if I were sitting here with an astronaut,

00:18:26.260 | I'd say, "Tell me something interesting

00:18:28.060 | "about being in space that I wouldn't know

00:18:29.420 | "from looking at pictures or videos of it."

00:18:32.180 | What is an example of maybe one of the more profound

00:18:36.340 | insight-stimulating moments from doing brain surgery?

00:18:40.380 | - I mean, every patient is different,

00:18:43.340 | so I'm always learning, and that's why I still enjoy it.

00:18:47.940 | That it's a challenge, and you have to think quickly.

00:18:51.260 | It's not simply mechanical,

00:18:55.580 | but for instance, a couple weeks ago,

00:18:57.860 | I had a patient who had a vascular malformation,

00:19:01.820 | which was located, we thought, right in her speech area.

00:19:06.820 | So in order to operate safely,

00:19:09.860 | first we did what's called a functional MR scan

00:19:12.600 | before surgery, and that gives us some idea

00:19:15.780 | of where the speech area is.

00:19:17.340 | We can map it out on an MR scan,

00:19:20.260 | and the way it's mapped out is

00:19:22.340 | we have the patient awake talk to us

00:19:27.640 | when they do the scan, and because there's a coupling

00:19:31.860 | between blood flow and the neuronal activity,

00:19:35.800 | when the speech area, the language area,

00:19:39.860 | is stimulated by talking,

00:19:41.800 | there's increased blood flow to that area,

00:19:44.700 | and we can see that on an MR scan.

00:19:46.540 | That's how the MR scan works.

00:19:48.660 | So we had some idea that this was very close,

00:19:51.300 | if not in the speech area,

00:19:53.480 | but the most accurate way of determining that

00:19:56.700 | is to operate on the patient with her awake.

00:20:01.540 | So we took, what we did was we sedate the patient.

00:20:04.760 | We don't put a tube down and induce general anesthesia.

00:20:08.300 | We numb up the scalp.

00:20:10.260 | We take off a piece of bone after cutting the scalp,

00:20:13.780 | open the membrane covering the brain called the dura,

00:20:17.220 | and then we allow the patient to wake up more

00:20:19.780 | from the sedation,

00:20:20.980 | and then what I did on this particular patient

00:20:25.260 | was to use a tiny stimulator, a little probe,

00:20:30.260 | and I can stimulate areas of her cortex with her awake

00:20:35.740 | and see if the stimulation impairs her ability

00:20:39.220 | to speak or understand language,

00:20:41.400 | and quite surprisingly, there was no activity

00:20:47.240 | in the corridor that I chose.

00:20:49.540 | Sometimes when we see an area

00:20:52.680 | that is involved with speech that's eloquent,

00:20:56.700 | we have to choose a different pathway

00:20:58.900 | to get to the underlying vascular problem,

00:21:01.860 | and so that's what we did in this case,

00:21:04.340 | and she talked to us the entire case.

00:21:07.060 | She told us about her daughter

00:21:08.900 | who was very involved in debate

00:21:14.660 | and all of her successes while we were operating,

00:21:17.320 | while I was taking out this vascular malformation

00:21:20.660 | under 20 magnification with very special instruments.

00:21:24.740 | I use a laser now which has a diameter

00:21:27.980 | of the fiber optic cable.

00:21:30.780 | The laser tip is 0.5 millimeters,

00:21:33.940 | so that I think is the gentlest way.

00:21:36.540 | Other times I've been surprised about brain function

00:21:42.180 | is operating deep in the brain

00:21:44.980 | is a part of the brain called the brainstem,

00:21:47.260 | which you know well.

00:21:48.620 | It's a small area that connects the thalamus.

00:21:52.920 | Those are the signals coming from the cortex,

00:21:54.900 | go through the thalamus to get down

00:21:56.740 | to the face, arm, and leg to move the muscles,

00:22:00.060 | and all the sensory information,

00:22:02.060 | which comes from the arms and legs and face,

00:22:04.580 | goes through the brainstem up to the thalamus

00:22:07.220 | and then to the cortex.

00:22:08.600 | In this area, although it's very small,

00:22:13.980 | are contained very closely packed fiber tracts

00:22:18.180 | and nuclei.

00:22:19.340 | Those are the cell bodies, very important neurons.

00:22:22.540 | And when I trained back in the '80s,

00:22:25.940 | we never operated in that area

00:22:28.060 | because we couldn't do it safely.

00:22:30.160 | With developments in computer technology

00:22:33.740 | and imaging and anesthesia,

00:22:36.300 | we can now find safe corridors to get into the brainstem,

00:22:41.300 | and sometimes we stimulate for other pathways,

00:22:44.740 | not language, but other pathways.

00:22:46.940 | And I'm continually amazed.

00:22:49.300 | This last week, I took out two vascular malformations,

00:22:54.300 | and they're not big.

00:22:57.220 | I mean, they measure between eight millimeters

00:23:00.660 | and a centimeter,

00:23:01.980 | but they can wreak havoc in the brainstem

00:23:04.140 | because it's such high-priced real estate,

00:23:06.300 | and these had bled.

00:23:07.800 | But I found a safe corridor to go through.

00:23:10.300 | I took it out, and I'm amazed

00:23:12.620 | that you hardly set the patients back in some cases

00:23:15.380 | because in the past, we would have clobbered the patients

00:23:18.300 | doing that.

00:23:19.380 | - Amazing.

00:23:20.220 | Yeah, it's remarkable to me how much can be done now

00:23:23.180 | with imaging, so visualizing the brain

00:23:25.180 | and being able to target a specific location.

00:23:27.580 | And you mentioned fiber optic cables.

00:23:29.780 | I've also heard of things like the gamma knife and lasers.

00:23:33.020 | So how much of neurosurgery nowadays

00:23:34.660 | is actually burrowing down through the brain

00:23:37.200 | to a given location to stimulate or remove tissue

00:23:40.800 | versus using these laser or fiber optic approaches

00:23:44.780 | to sort of triangulate and get to something

00:23:46.780 | without having to basically drill down through the brain?

00:23:49.440 | - Right.

00:23:50.280 | Neurosurgery is becoming much less invasive.

00:23:54.140 | And this is something that I really tried to push

00:23:56.460 | when I was a chair of the department

00:23:58.460 | for 25 years at Stanford.

00:24:00.120 | So minimally invasive techniques include

00:24:04.100 | operating through the vessels, right?

00:24:08.560 | So now, I don't do this myself, but my colleagues,

00:24:11.660 | some of whom are neurosurgeons,

00:24:12.900 | some are interventional radiologists,

00:24:15.100 | they can go through the groin in the femoral artery

00:24:17.620 | or through the radial artery.

00:24:19.980 | They can thread a catheter backwards into the brain.

00:24:24.700 | From the groin, they can go up into the aorta,

00:24:28.300 | then up into the carotid artery.

00:24:30.700 | From there, they can go up into the brain arteries,

00:24:33.620 | the middle cerebral artery,

00:24:35.380 | and they can treat some of the hemorrhagic problems

00:24:39.420 | like aneurysms by deploying thrombogenic coils there

00:24:43.700 | or new devices.

00:24:45.740 | They can pull clots out if there's an acute stroke

00:24:49.220 | from a clot in an artery in the brain.

00:24:51.900 | It's really quite impressive.

00:24:54.300 | Then we and others have developed techniques

00:24:59.140 | to use focus radiation on the brain,

00:25:03.740 | and that's called radiosurgery.

00:25:05.860 | So examples of that are Gamma Knife,

00:25:09.300 | Cyber Knife was invented at Stanford

00:25:11.380 | by one of my colleagues, actually,

00:25:13.540 | and this uses beams of radiation.

00:25:17.180 | Gamma Knife uses a cobalt source,

00:25:19.340 | multiple sources of cobalt.

00:25:21.980 | The Cyber Knife uses X-rays.

00:25:25.780 | When I started, I was very involved

00:25:28.580 | with using cyclotron-generated heavy particles

00:25:32.100 | like helium and proton, and they can be focused.

00:25:36.220 | And the advantage of this is you don't have

00:25:38.420 | to open the skull.

00:25:40.300 | You focus it on a very small area,

00:25:43.140 | and you can eliminate vascular malformations

00:25:47.020 | called arteriovenous malformations, tumors.

00:25:50.460 | You can even use it for some pain conditions

00:25:52.780 | like trigeminal neuralgia.

00:25:54.500 | It's not risk-free because even though radiation

00:25:58.900 | doesn't require opening the skull,

00:26:02.700 | it still is a form of energy that's damaging.

00:26:05.100 | That's how it works.

00:26:05.980 | It causes, for the AVMs,

00:26:07.500 | it gradually clots off the blood vessels,

00:26:10.260 | but it's much easier and much safer

00:26:13.100 | than some of the invasive techniques that we use.

00:26:15.980 | We operate now through tiny openings,

00:26:18.140 | even when we do open surgery.

00:26:20.620 | When I trained, we used to shave the whole head.

00:26:23.980 | We would open a huge area of the skull.

00:26:27.100 | Now we operate through tiny, very small areas.

00:26:31.500 | When I take out vascular malformations

00:26:34.420 | in the brainstem, for instance,

00:26:36.020 | I sometimes operate through openings

00:26:39.060 | in the side of the brainstem that are two to three millimeters.

00:26:42.740 | - Wow.

00:26:43.580 | - Another form of noninvasive treatment

00:26:47.940 | that neurosurgeons use is called focused ultrasound.

00:26:52.140 | Again, you don't have to open the skull.

00:26:54.740 | It focuses sound waves on areas of the brain.

00:26:59.620 | We're using that to treat essential tremor.

00:27:04.300 | Or Parkinson's disease,

00:27:08.540 | it's starting to be used for treating tumors.

00:27:10.780 | So these are all advances that were not present

00:27:15.620 | when I trained.

00:27:17.100 | Another way of treating minimally invasive,

00:27:20.060 | although it still requires a hole in the head,

00:27:21.900 | is to put in an electrode and stimulate the brain.

00:27:26.900 | So that was first used for treating Parkinson's disease,

00:27:31.860 | very effective for medically intractable Parkinson's.

00:27:35.740 | It's used to treat chronic pain.

00:27:38.700 | Recently, it was shown to be beneficial for epilepsy.

00:27:43.140 | In fact, the two major trials,

00:27:45.420 | prospective randomized trials that were done,

00:27:48.140 | were led by physicians, neurologists at Stanford,

00:27:51.900 | and showed the benefit of stimulation of the brain

00:27:55.820 | to treat a very difficult epilepsy.

00:28:00.020 | So this, I think, is going to be the future,

00:28:02.220 | is more and more minimally invasive.

00:28:05.060 | In fact, we're using some of these techniques

00:28:07.160 | to even treat psychiatric disorders,

00:28:10.060 | like depression, obsessive compulsive behavior.

00:28:12.820 | - Incredible.

00:28:13.820 | I should have asked this earlier,

00:28:15.140 | but TIAs, transient ischemic attacks.

00:28:19.140 | I think most people assume or know

00:28:22.220 | that the symptoms of stroke include sudden weakness,

00:28:25.980 | maybe hemiparalysis of the face,

00:28:27.740 | confusion, slurring of the words.

00:28:29.860 | Of course, these symptoms can be the consequence

00:28:31.660 | of other things as well.

00:28:32.940 | What are some of the symptoms of transient ischemic attacks?

00:28:37.260 | And is there anything that people can take

00:28:39.620 | for transient ischemic attacks?

00:28:41.660 | And I, of course, would love for you to inform us

00:28:44.500 | what a transient ischemic attack is.

00:28:47.300 | - Right, so a transient ischemic attack, or TIA,

00:28:50.380 | is a reversible stroke.

00:28:52.540 | It results in a temporary loss of function,

00:28:57.420 | such as inability to move,

00:29:00.940 | partial paralysis or complete paralysis,

00:29:03.180 | but then it resolves.

00:29:04.480 | Inability to speak, visual problems,

00:29:08.060 | double vision, blurred vision, loss of vision.

00:29:12.360 | It can cause slurred speech

00:29:15.860 | or difficulty understanding language,

00:29:17.940 | imbalanced problems, walking, even cognitive problems.

00:29:21.580 | So it can vary depending on what part of the brain

00:29:24.380 | it affects.

00:29:26.060 | In the past, it was defined as a neurologic deficit

00:29:30.580 | due to lack of blood flow that lasted less than 24 hours.

00:29:34.580 | But now that we have such sophisticated imaging,

00:29:38.300 | like MR scan, some of these patients who have a TIA,

00:29:42.220 | what would have been considered a TIA before,

00:29:44.220 | lasting minutes or up to 24 hours,

00:29:47.700 | on MR scan have been shown to have a little stroke.

00:29:51.140 | So now the definition is a little different.

00:29:53.900 | If you do an MR scan and it shows a new abnormality,

00:29:58.780 | a new stroke, then it's called a stroke rather than a TIA.

00:30:02.740 | So there's a little overlap there,

00:30:05.460 | but it's a temporary loss of neurologic function

00:30:09.940 | due to lack of blood flow, or in some cases, a hemorrhage.

00:30:14.940 | - My understanding is that people can also have strokes

00:30:17.260 | in their spinal cord, because spinal cord tissue

00:30:20.880 | is, after all, central nervous system tissue.

00:30:22.940 | I think most people don't realize this,

00:30:24.120 | but the tail end of the brain, the brainstem,

00:30:27.740 | as we were talking about before,

00:30:29.140 | essentially extends down the spinal column.

00:30:32.580 | It's more like a long tail, right?

00:30:36.100 | Down to the base of the pelvis, really.

00:30:40.900 | So we call it the spinal cord, but it's all brain.

00:30:44.180 | It's contiguous with the brain.

00:30:45.740 | So how often do you observe spinal strokes

00:30:50.540 | and what are some of the symptoms of spinal stroke?

00:30:52.860 | - Yeah, it's much less common

00:30:55.180 | than a stroke involving the brain,

00:30:58.580 | probably because there's less tissue involved.

00:31:02.380 | The spinal cord is supplied by an anterior spinal artery.

00:31:07.380 | That's an artery on this side, and by two-

00:31:11.500 | - So for those listening, sorry,

00:31:12.660 | it would be on the stomach side of the body, yeah.

00:31:16.960 | - And it's supplied by two arteries,

00:31:20.100 | posterior spinal on the backside.

00:31:23.000 | So if there's an interruption to blood flow

00:31:26.260 | in any of those arteries,

00:31:28.020 | it can cause death of tissue in the spinal cord,

00:31:31.860 | and that would result in a neurologic deficit,

00:31:34.740 | depending on where it is.

00:31:37.020 | So if it occurred on the stomach side,

00:31:40.720 | that whole artery which supplies

00:31:42.820 | the two-thirds of the spinal cord on the stomach side,

00:31:48.820 | and it involved both sides of the spinal cord,

00:31:52.460 | it would cause paralysis of both legs,

00:31:56.300 | and a partial sensory deficit

00:32:00.220 | would cause loss of pain and temperature,

00:32:01.820 | 'cause that's where those pathways are.

00:32:04.380 | If the problem was on the backside of the cord,

00:32:07.820 | it would cause a problem potentially

00:32:10.580 | with a light touch sensation in the legs.

00:32:15.540 | If it was below the cervical region,

00:32:20.540 | and problems with what's called proprioception,

00:32:23.700 | that's the ability to recognize

00:32:25.300 | where your position of your joints is.

00:32:28.240 | So it depends on where it is.

00:32:30.340 | Some of the vascular problems I deal with

00:32:33.860 | actually do involve the spinal cord,

00:32:36.700 | and you can develop other problems there.

00:32:39.440 | For instance, you can have a direct connection

00:32:42.580 | between a abnormal artery and a vein in the spinal cord,

00:32:47.580 | which doesn't cause a typical stroke

00:32:50.340 | by blocking blood flow,

00:32:51.600 | but it causes more of that venous problem we discussed,

00:32:54.980 | where there's so much blood going directly

00:32:57.500 | from the artery to the vein, bypassing the capillaries,

00:33:01.520 | that the veins become engorged.

00:33:03.880 | The blood can't get out of the spinal cord,

00:33:06.540 | and the spinal cord becomes congested,

00:33:08.840 | and patients can present with problems,

00:33:11.560 | walking or sensory problems.

00:33:14.760 | If the spinal cord is involved

00:33:18.240 | in the cervical region up high,

00:33:20.440 | then the arms can be involved as well.

00:33:22.560 | - I see.

00:33:23.400 | I should have asked this earlier,

00:33:24.520 | but is there any relationship between alcohol intake

00:33:27.000 | and the propensity for stroke or hemorrhage

00:33:29.680 | or any of these other things?

00:33:30.520 | - Yeah, that's a good question.

00:33:31.580 | Yes, there is.

00:33:36.720 | People who indulge or overindulge

00:33:39.360 | are at risk for developing stroke problems.

00:33:44.560 | So it's another contributory factor,

00:33:48.160 | which can promote problems with the blood vessels,

00:33:52.060 | clots, but also hemorrhage.

00:33:56.160 | So it can make the blood vessels more fragile.

00:33:59.440 | Another factor I see commonly

00:34:01.300 | in patients who develop aneurysms,

00:34:03.960 | those are blisters on the blood vessels in the brain,

00:34:06.920 | and they're like little balloons,

00:34:08.360 | and as they enlarge,

00:34:09.440 | they rupture just like a balloon can burst.

00:34:11.640 | Some of the patients I see are not just smokers,

00:34:17.400 | but indulge in other drugs.

00:34:19.880 | So cocaine, methamphetamines,

00:34:22.740 | markedly increase the risk of developing these aneurysms

00:34:27.200 | or developing hemorrhage, bursting of a blood vessel.

00:34:30.240 | - And is that because those drugs

00:34:31.520 | tend to increase blood pressure during their use?

00:34:34.080 | - It's because they damage the vessels,

00:34:38.540 | and they also cause hypertension.

00:34:41.360 | Yes, it's both factors.

00:34:42.840 | So when I operate on these patients

00:34:46.120 | and looking at the vessels,

00:34:47.580 | they are ragged, they're very thin.

00:34:52.180 | They're not normal vessels.

00:34:53.780 | They lack structural integrity.

00:34:56.000 | So it contributes to the development

00:34:57.940 | of poor vessel integrity.

00:35:00.520 | And drugs like cocaine and methamphetamine

00:35:03.200 | can jack the blood pressure up,

00:35:05.040 | and that could cause a hemorrhage

00:35:06.760 | in these problematic vessels, yes.

00:35:10.360 | - So it sounds like the message is clear.

00:35:12.760 | Avoid cocaine use, avoid methamphetamine use,

00:35:16.200 | and avoid excessive alcohol intake,

00:35:19.200 | if you want to avoid stroke.

00:35:20.680 | - Right, and throw smoking in there too.

00:35:23.880 | - It's interesting because for a lot of years,

00:35:25.560 | there was so much discussion about red wine

00:35:27.860 | being good for heart health.

00:35:29.360 | Now it's debated.

00:35:30.700 | The moment I say that,

00:35:31.540 | people will send a bunch of studies that say yes.

00:35:33.580 | My stance on the more recent data

00:35:35.880 | is that if you had to pick,

00:35:36.900 | you drink less or not drink as opposed to drink.

00:35:40.120 | But I'm curious what your take is on this.

00:35:41.480 | - Well, you know, this is interesting,

00:35:42.880 | and I'm always quite amazed

00:35:45.440 | at the way people change their behavior

00:35:47.920 | based on one study that comes out,

00:35:49.840 | even if it's a good study.

00:35:50.920 | So yes, it used to be

00:35:54.960 | considered beneficial if you drank red wine.

00:35:59.320 | And then for a while,

00:36:01.880 | studies showed any wine was beneficial in moderation.

00:36:05.520 | And that used to be two drinks a day for men,

00:36:10.360 | one drink a day for women.

00:36:11.920 | And in the latest studies,

00:36:13.240 | which have been surfacing this year,

00:36:15.600 | suggest no alcohol is good.

00:36:18.840 | But next year, it may be that we're back to,

00:36:22.440 | oh, wine is the best thing you can do in moderation

00:36:26.000 | for your brain and heart health.

00:36:28.680 | - Yeah, it's tricky.

00:36:29.680 | My read of the data,

00:36:31.800 | and here I mean the data across multiple,

00:36:34.180 | certainly not every study,

00:36:35.400 | but multiple studies,

00:36:36.240 | is that zero to two drinks per week

00:36:39.880 | seems to be the range that everyone agrees is safe,

00:36:42.680 | at least for non-alcoholic adults.

00:36:44.460 | And then once you get out past two drinks per week

00:36:47.640 | is when it gets into the gray zone

00:36:49.480 | where some people say it's good,

00:36:50.940 | some people say it's neutral,

00:36:52.000 | some people say it's bad.

00:36:53.380 | But that once you get up past

00:36:55.400 | four or five servings of alcohol per week,

00:36:58.360 | it's pretty clear to me,

00:36:59.320 | it's not a good situation.

00:37:00.520 | - Well, that was the prevailing theory until this year.

00:37:04.120 | And I don't know if you've kept up,

00:37:05.720 | but in the past few months,

00:37:08.180 | there have been several articles published saying,

00:37:10.680 | no wine, no alcohol is good.

00:37:14.920 | But then you have to balance that against the fact

00:37:17.660 | that alcohol for many people tends to relieve stress.

00:37:21.760 | So if you're relieving stress,

00:37:24.880 | maybe it counteracts any adverse effects.

00:37:27.760 | So complicated issue.

00:37:29.280 | But my theory is moderation is the key to life

00:37:34.280 | and happiness also we know promotes longevity.

00:37:41.620 | - Absolutely, I agree with you.

00:37:43.000 | I'm not heavy-handed about the alcohol thing.

00:37:44.680 | I always just say, do as you wish,

00:37:47.080 | but know what you're doing.

00:37:49.320 | And I think many people who heard our podcast episode

00:37:54.320 | about alcohol, who stopped drinking alcohol

00:37:57.200 | or who elected to drink less did so, I'm told,

00:38:00.340 | because they really didn't enjoy it that much to begin with.

00:38:04.240 | So it more or less gave them permission to drink less,

00:38:06.960 | not that they needed it, but they took it.

00:38:08.960 | Anyway, I think it's a really interesting area.

00:38:10.880 | As you mentioned, it probably lowers stress.

00:38:13.640 | It probably also disrupts patterns of sleep

00:38:16.080 | in the gut microbiome.

00:38:17.080 | So there's, you can't escape in biology.

00:38:19.440 | There's always some modulatory influence on something else.

00:38:23.400 | - Exactly.

00:38:24.840 | - I'd like to take a brief break

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00:39:55.560 | Speaking of lifestyle factors,

00:39:58.960 | anytime we hear about traumatic brain injury or concussion,

00:40:01.920 | people immediately seem to think about football.

00:40:04.920 | But I'm told by colleagues of ours in neurosurgery

00:40:08.380 | at Stanford and in neuroengineering

00:40:11.160 | that most head injuries are not from football.

00:40:13.840 | They're not even from sport.

00:40:14.760 | They're from construction work accidents.

00:40:17.080 | They're from car accidents.

00:40:18.660 | What is your take on, you know, somebody, let's say,

00:40:23.480 | God forbid, gets rear-ended in a car accident.

00:40:26.640 | Maybe gets whiplash.

00:40:27.520 | Maybe they're feeling a little off.

00:40:28.560 | Like maybe they have a minor concussion.

00:40:29.840 | Maybe there was some movement of the brain

00:40:32.560 | that wasn't good.

00:40:34.080 | What's the going consensus on how to deal with that?

00:40:37.080 | Sleep more,

00:40:39.080 | but then they tell you not to sleep excessively.

00:40:41.680 | Should people take blood thinning agents?

00:40:43.820 | I mean, obviously avoid alcohol

00:40:45.800 | or certainly don't get another head injury anytime soon.

00:40:49.200 | But, you know, what do we know about TBI and concussion

00:40:52.100 | that can help people move through that period

00:40:55.320 | in the weeks and months afterwards

00:40:57.400 | where it's really scary, you know,

00:40:58.880 | if you've ever had a hard head hit, you know,

00:41:00.600 | and they go, they might scan you.

00:41:02.160 | They might not see a bleed,

00:41:03.620 | but it's kind of scary when you feel a little bit off

00:41:06.060 | because you've been hit in the head.

00:41:07.280 | - Yeah, it's a great question.

00:41:08.500 | And there's a lot of interesting concussion now.

00:41:11.640 | I got very involved in this back in the '90s

00:41:14.560 | 'cause I was the 49ers neurosurgeon for a decade

00:41:18.860 | from 1990 to 2000.

00:41:21.780 | - How were they doing at that point?

00:41:23.200 | I remember the dynasty of the '80s

00:41:24.800 | or the '90s are good.

00:41:25.840 | - Oh, they were in Super Bowl contention.

00:41:28.680 | In fact, I took care of Steve Young.

00:41:31.080 | - Yeah, he's a local guy.

00:41:32.280 | - Yeah, Steve's a great guy.

00:41:33.640 | And Steve, a really smart guy.

00:41:37.880 | In fact, he has a law degree from Brigham Young.

00:41:42.880 | Steve was quarterback then

00:41:45.580 | and they were in Super Bowl contention

00:41:47.540 | and Steve had had some concussions

00:41:51.320 | and I actually sent him back to play when he recovered.

00:41:55.520 | So you can examine someone

00:41:57.460 | and get a decent idea

00:42:01.820 | of how they're recovering from a concussion.

00:42:04.700 | Steve unfortunately had a bad concussion at one point

00:42:09.700 | and he ended up retiring,

00:42:11.840 | which was the smartest thing I think for him in the end.

00:42:14.480 | And he's become very involved with studying concussions

00:42:18.120 | and trying to figure out better ways to diagnose them,

00:42:23.120 | prevent the sequelae for football players,

00:42:26.680 | including changes in equipment

00:42:28.600 | and in tackling and that kind of thing.

00:42:33.200 | But concussion is, we've learned a lot since the 1990s.

00:42:37.000 | At that time, concussion was not known,

00:42:42.000 | even repeated concussion, to cause CTE,

00:42:46.520 | chronic traumatic encephalopathy in football players.

00:42:49.000 | CTE, which became a hot topic, was known only in boxers.

00:42:54.000 | So I became very well informed at the time about concussions

00:42:58.840 | and there was surprisingly little known.

00:43:02.600 | Soccer players had a high incidence of concussion

00:43:05.960 | at that time.

00:43:06.800 | It wasn't known if there were long-term sequelae.

00:43:09.040 | And usually there are not long-term sequelae

00:43:11.920 | as long as you don't get repeated concussions.

00:43:16.400 | So now what we generally recommend

00:43:22.640 | if someone has a concussion,

00:43:24.220 | we usually get an MR scan if it's severe.

00:43:28.280 | MR scans usually don't show anything.

00:43:32.000 | They would show a contusion

00:43:33.480 | if there's any bruising of the brain,

00:43:35.700 | but they don't show the molecular abnormalities

00:43:40.560 | that occur with a concussion.

00:43:42.520 | So the best way to figure out how severe it is

00:43:46.000 | and when a person has recovered

00:43:48.560 | is to do more sophisticated neurologic testing.

00:43:52.240 | Eye tracking is a very sensitive way

00:43:55.840 | to detect problems with the brain after a concussion

00:44:00.840 | because you won't track as well.

00:44:03.600 | And in fact, many sports, football, hockey,

00:44:07.840 | are incorporating pre-season eye tracking testing.

00:44:12.840 | - I see, to get a baseline.

00:44:15.360 | - To get a baseline.

00:44:16.560 | Of course, some of the players will game the system

00:44:20.280 | because they still don't wanna be taken out.

00:44:22.720 | So they may try to perform not as well as they could.

00:44:27.280 | - On their eye tracking?

00:44:28.480 | - Yeah, on their--

00:44:29.320 | - I see, they throw the test.

00:44:30.520 | - They throw the test so their baseline is,

00:44:32.480 | I mean, I don't think that's very common,

00:44:34.680 | but that's a way you can game the system.

00:44:36.160 | But as long as it's performed well,

00:44:38.400 | that's a very good way of detecting

00:44:41.320 | subtle problems with the brain.

00:44:44.040 | You're a vision scientist,

00:44:45.320 | so you understand how important all the circuits are

00:44:51.720 | in terms of, and the visual system is unique

00:44:55.560 | because it tests the brain from the retina

00:45:00.040 | all the way back to the occipital lobe.

00:45:02.920 | So it's the whole longitudinal access

00:45:05.400 | of the brain that's being tested.

00:45:07.720 | - Yeah, I'm always struck by,

00:45:09.520 | when I see these newsreel highlights of,

00:45:12.440 | a player goes down, they stay down,

00:45:15.400 | and then they're helped up and everyone cheers,

00:45:20.080 | and then they might hobble off, take a few moments,

00:45:22.040 | and then how are they gauging the decision

00:45:24.080 | to put the person back in?

00:45:25.160 | And the reason it's perplexing to me

00:45:28.320 | how they would determine that is that,

00:45:30.440 | you and I both know that the neurons,

00:45:32.240 | the nerve cells in the brain very likely could be injured,

00:45:36.280 | maybe even on their way to death after a head injury,

00:45:40.040 | but that the actual dying off of the tissue

00:45:42.600 | could take several minutes, hours, maybe even days.

00:45:45.280 | So putting someone back in to get hit more,

00:45:49.880 | seems really risky, but at the same time,

00:45:52.440 | that's their profession, that's their choice.

00:45:54.320 | And so you don't necessarily wanna make the decision

00:45:57.480 | to take someone out of a game or a job,

00:46:00.720 | or have them stop driving

00:46:01.960 | if they don't actually need to stop.

00:46:03.840 | So it's a tricky thing.

00:46:04.960 | - It is tricky, and I think we have better methods of,

00:46:08.880 | even at the, if you're talking about sports,

00:46:11.720 | on the sideline of doing testing,

00:46:13.840 | there are neurosurgeons there now

00:46:16.880 | who are part of the process.

00:46:18.620 | As far as recovering in general,

00:46:23.380 | it's good to not stress the brain,

00:46:25.880 | but total absence of sensory information,

00:46:30.820 | sensory deprivation for long periods is not a good idea.

00:46:33.900 | - Or just staying home in the dark with sunglasses on,

00:46:36.220 | also not a good idea.

00:46:37.180 | - Exactly.

00:46:38.020 | So you wanna make sure the brain still has input,

00:46:40.340 | but you don't wanna overstress it

00:46:42.420 | when you're recovering from a concussion.

00:46:45.260 | - Sounds like doing all the things

00:46:46.780 | to keep blood pressure relatively low,

00:46:48.980 | LDL cholesterol relatively low.

00:46:52.060 | So interesting what you said earlier,

00:46:53.440 | that statins might be vascular protective

00:46:56.460 | even in the absence of high cholesterol.

00:46:59.260 | - Yeah, there's a lot of good evidence for that.

00:47:00.780 | In fact, some studies have suggested

00:47:02.540 | that taking statins reduces the risk of cognitive decline,

00:47:06.300 | including conditions like Alzheimer's.

00:47:08.740 | - Interesting.

00:47:09.580 | I know that statins are a bit of a controversial topic

00:47:12.780 | among listeners because some people report,

00:47:15.700 | I think I have this right,

00:47:16.900 | that statins can give them a kind of a brain fog

00:47:19.100 | if they take the wrong one or excessive amounts.

00:47:21.500 | I'm not challenging what you're saying.

00:47:24.100 | - No, no, no, it's still controversial.

00:47:25.100 | - I just hear the shouts in the comment section.

00:47:28.180 | I don't take a statin, but my cholesterol is in check,

00:47:30.940 | but I'm hearing more and more

00:47:33.460 | about some of these benefits of statins.

00:47:35.740 | - Yeah, yeah, and the information is still emerging.

00:47:38.900 | For a traumatic brain injury in general,

00:47:42.700 | not a good idea to take an aspirin

00:47:46.220 | as opposed to a stroke or a TIA.

00:47:48.940 | - Where you would want to take an aspirin.

00:47:50.500 | - Right, right, because if you have injuries,

00:47:52.260 | say you have a contusion to the brain

00:47:54.580 | and there's some traumatic damage,

00:47:58.100 | taking a blood thinner might cause that to worsen

00:48:00.820 | or cause a hemorrhage.

00:48:02.540 | - What about caffeine?

00:48:03.460 | Is there any evidence that caffeine

00:48:04.940 | can increase stroke or ischemia?

00:48:06.580 | I like coffee and I like yerba mate tea,

00:48:09.020 | so I'd be reluctant to give it up,

00:48:10.660 | but I consume it in moderation.

00:48:12.100 | Is there any direct relationship there?

00:48:13.860 | - I don't know any relationship,

00:48:15.780 | unless you're taking so much

00:48:17.980 | that your blood pressure is sky high.

00:48:20.060 | - My blood pressure tends to be pretty low.

00:48:20.980 | - Lots of benefits evidently to caffeine

00:48:25.300 | in terms of health.

00:48:27.700 | - I agree with you there.

00:48:29.020 | I have a question about something

00:48:31.420 | that many people are starting to do now,

00:48:34.780 | which is to get exploratory MRI.

00:48:38.800 | I actually did one of these.

00:48:40.420 | I wasn't gifted one.

00:48:41.580 | I just decided to bite the bullet and pay for it,

00:48:43.820 | is a whole body scan.

00:48:44.980 | They put me in the tube, did a MRI,

00:48:46.780 | get everything from tip to toe.

00:48:48.620 | And I learned a few things.

00:48:50.060 | I learned that I have like a slight,

00:48:51.780 | I think it's L3 or L4 disc bulge.

00:48:54.140 | That explained a little bit of like pseudo sciatica

00:48:57.020 | and I've been able to work around that

00:48:59.500 | and keep that strong.

00:49:00.940 | I learned that fortunately for me,

00:49:03.280 | I only have one white spot on the brain.

00:49:05.340 | I was told that you could have one per decade.

00:49:07.340 | I'm nearing 50, so I feel very lucky there,

00:49:09.560 | especially given that I've hit my head a few times,

00:49:12.140 | skateboarding and doing martial arts and things like that.

00:49:14.320 | But, so I feel lucky,

00:49:16.700 | but I also know people that go in for these scans

00:49:19.380 | and get the report that, you know,

00:49:21.740 | they have a growth of some sort

00:49:24.400 | or they have multiple white spots

00:49:26.020 | as they're called on the brain,

00:49:26.980 | which is kind of damage to tissue, the neural tissue.

00:49:30.740 | You know, what is your thought

00:49:31.660 | on these exploratory/preventative scans?

00:49:35.220 | Do you think they're useful?

00:49:37.340 | Do you feel like they cause undue concern?

00:49:40.000 | I mean, this is a new thing,

00:49:40.920 | people going out and getting their brain scanned.

00:49:43.580 | - Yeah, and people are getting total body scans.

00:49:45.480 | So I think there are benefits and risks involved.

00:49:49.120 | So the benefit is that you might pick up

00:49:52.160 | something that should be treated,

00:49:53.720 | like an early cancer or a large aneurysm in the brain,

00:49:58.720 | which would have a higher chance to bleed.

00:50:02.000 | But many times, and I see patients all the time

00:50:04.880 | who are referred for a tiny aneurysm,

00:50:08.340 | blister on a blood vessel in the brain

00:50:11.280 | that was found incidentally on a total body scan.

00:50:14.500 | And these aneurysms, which can be one or two millimeters,

00:50:18.860 | sometimes we don't even consider those as real aneurysms,

00:50:21.980 | they don't need to be treated in most cases.

00:50:26.360 | And so it's a little controversial

00:50:31.080 | because people can be worried about them,

00:50:32.800 | even if they're reassured.

00:50:34.720 | Other examples are you find something in the brain

00:50:37.520 | or elsewhere in the body, not sure what it is.

00:50:40.240 | And then in order to determine what it is,

00:50:43.000 | patients start having more invasive biopsies and tests,

00:50:46.120 | which can lead to what we call iatrogenic injuries.

00:50:50.120 | That's, iatrogenic is caused by the physicians.

00:50:53.840 | So I think you have to be very thoughtful

00:50:56.560 | when you interpret the results of these total body

00:51:01.560 | or even brain scans.

00:51:04.760 | And I would recommend talking with a specialist about it

00:51:09.480 | if you're concerned.

00:51:13.000 | But people wonder, I have this,

00:51:16.680 | we were discussing it earlier today actually

00:51:19.800 | with one of your colleagues.

00:51:21.640 | And what if you're found to have a 1.75 millimeter aneurysm,

00:51:26.640 | if it's really even an aneurysm,

00:51:29.220 | should you change your lifestyle?

00:51:31.200 | And for something like that, I would recommend, no,

00:51:34.280 | you should forget about it, get a follow-up scan,

00:51:37.400 | but you may very well live and die with this little blister

00:51:41.920 | that is of no consequence.

00:51:43.160 | So as I say, I think you have to be careful

00:51:46.800 | about how you interpret and how you act on these findings.

00:51:51.800 | - Maybe we can talk about lifestyle factors

00:51:55.720 | because I think anyone listening to this is gonna think,

00:51:57.920 | I don't want a stroke, I don't want transient ischemic attack,

00:52:00.720 | I don't want hemorrhage, I don't want any of this stuff.

00:52:02.960 | And we already discussed a little bit

00:52:04.240 | about how what's good for your heart

00:52:05.480 | generally is good for the brain.

00:52:07.280 | But I think most people strive to eat well,

00:52:10.480 | meaning not excessively, also not undereat,

00:52:13.340 | to hopefully eat a lot of unprocessed

00:52:17.600 | or minimally processed foods and to avoid smoking perhaps,

00:52:22.600 | avoid alcohol in excess, avoid hard drugs, get exercise.

00:52:30.360 | And so, I think people generally try

00:52:32.360 | and do all these things, get good sleep, et cetera.

00:52:34.920 | But at some level, I think everyone also wants to know,

00:52:38.720 | when are they in their safest kind of shape

00:52:44.320 | for avoiding a stroke?

00:52:45.560 | Is there sort of a blood pressure cutoff

00:52:48.240 | where we could say, okay, if you keep your blood pressure,

00:52:50.600 | resting blood pressure below blank, you're doing pretty well.

00:52:54.600 | And if your cholesterol is below blank,

00:52:57.260 | you're doing pretty well.

00:52:58.100 | And then you just, while keeping moderation in mind,

00:53:02.100 | try and live a life that reduces the probability

00:53:05.860 | of getting a stroke or some other

00:53:09.060 | blood-related neural attack.

00:53:11.560 | - Well, I think it has to be individualized to some extent.

00:53:14.300 | And over time, the standards and the guidelines have changed.

00:53:18.740 | It used to be, if your systolic blood pressure,

00:53:21.820 | that's the upper number, was under 130, 130 or under,

00:53:27.220 | that was considered normal and it would not lead to problems.

00:53:30.820 | Now, the guidelines suggest that 120 or lower is better

00:53:35.820 | in large studies.

00:53:39.380 | But as an example, when my blood pressure gets under 120,

00:53:44.380 | I feel lightheaded.

00:53:46.660 | In fact, I had an event about 15 years ago

00:53:51.580 | when I was overdoing it, like I shouldn't have been.

00:53:55.700 | - Overdoing exercise or overdoing?

00:53:56.900 | - Overdoing everything.

00:53:57.860 | I was in my, I was fifth.

00:53:59.260 | - A Stanford faculty member that overdoes something?

00:54:01.460 | That was a joke that among Stanford faculty.

00:54:03.140 | - I was 56 and I operated all day in two operating rooms.

00:54:08.140 | I got done early, it was in the spring,

00:54:13.460 | and I took a run up to the dish.

00:54:15.580 | And then I took a red-eye to Houston for a meeting.

00:54:18.780 | And I emailed on the flight, got an hour or two of sleep,

00:54:22.140 | went to the meeting, was fine.

00:54:25.100 | It was a stroke meeting with a bunch of scientists,

00:54:28.100 | neurologists and scientists who were about 120 people.

00:54:33.220 | There were two neurosurgeons there, plus me.

00:54:36.100 | And drank some coffee.

00:54:38.100 | At noon, I went for a run 'cause I like running.

00:54:42.060 | And at that day in Houston,

00:54:44.180 | it was 90 degrees and 85% humidity.

00:54:49.180 | And got back, had a glass of tea,

00:54:54.180 | went back to the meeting, had some more coffee.

00:54:56.460 | And then as the afternoon session opened up,

00:54:59.180 | I started to feel lightheaded.

00:55:01.260 | And next thing I know, I'm looking up at the chandelier

00:55:04.620 | and they're shouting stroke, cardiac arrest, seizure,

00:55:09.620 | and they're starting to pump on my chest.

00:55:12.500 | So they rushed me to the hospital

00:55:14.820 | where I had a simultaneous workup

00:55:18.060 | for cardiac arrest and stroke.

00:55:20.860 | And after, I'll make the story short,

00:55:24.260 | after $100,000 workup, it was determined I had a faint

00:55:29.260 | because I was overdoing it.

00:55:33.420 | So since then, now I try to get seven

00:55:37.500 | to eight hours sleep a night.

00:55:38.740 | - Great, that's clearly the bedrock of health.

00:55:40.700 | - So I increased.

00:55:41.540 | I used to get three to five hours sleep a night.

00:55:44.220 | Now I get seven to nine if I can do it.

00:55:47.340 | Cut back on coffee, on caffeine.

00:55:50.700 | And I don't push myself to exercise like I used to

00:55:55.580 | if I'm feeling a little fatigued.

00:55:57.460 | I'm on an antihypertensive agent,

00:55:59.480 | but I actually don't take it every day

00:56:01.780 | because for me, it's better to have a pressure 125 to 135.

00:56:06.780 | And it's true for some of my patients.

00:56:10.660 | If you've got some disease in your arteries,

00:56:13.580 | you may not wanna have such a low blood pressure.

00:56:15.700 | So I would individualize it.

00:56:17.120 | But in general, you wanna take care of your body

00:56:20.780 | like I've learned and probably,

00:56:23.500 | maybe you've learned over time.

00:56:25.180 | - I'm learning.

00:56:26.020 | I mean, this is very interesting.

00:56:26.980 | I tend to have low blood pressure.

00:56:29.180 | It sort of runs in my family to have low blood pressure.

00:56:31.980 | I can definitely relate to the hard driving

00:56:38.340 | ambition phenotype.

00:56:40.700 | I think it's worth people hearing this

00:56:42.740 | because it's characteristic of a lot of people

00:56:44.540 | in high intensity professions.

00:56:46.100 | And I made the joke about Stanford faculty,

00:56:47.800 | but it's true.

00:56:49.660 | I think that if you're ambitious,

00:56:50.940 | you tend to overdo a bit more.

00:56:52.860 | That's something I'm certainly working on.

00:56:54.500 | And I've run a very busy life

00:56:57.220 | and learning to slow down, prioritize sleep,

00:57:00.460 | prioritize meditation, non-sleep deep rest

00:57:03.740 | is something I've benefited from a lot.

00:57:05.740 | Journaling, things of that sort

00:57:07.140 | that really just kind of slow the pace.

00:57:08.940 | I think that in the landscape of health optimization,

00:57:13.660 | we can often put ourselves into modes of excess

00:57:16.840 | in the other direction,

00:57:17.980 | meaning doing so much to try and avoid issues with health

00:57:23.240 | that we end up creating issues with health.

00:57:25.100 | But yeah, certainly reducing caffeine intake

00:57:27.020 | and prioritizing sleep are key.

00:57:29.160 | So I appreciate that you shared that story.

00:57:30.820 | So if somebody has naturally low blood pressure

00:57:34.020 | and starts to feel a bit,

00:57:36.000 | let's just say kind of sleepy or woozy in the afternoon,

00:57:38.660 | would you recommend that they obviously

00:57:41.540 | not take a pressure-lowering drug,

00:57:44.920 | but that they add a bit of salt to their diet,

00:57:48.260 | that they feel free to exercise less?

00:57:53.260 | I'm a little bit confused.

00:57:55.260 | I also love to run and do resistance training.

00:57:57.180 | - Well, I would recommend they take their blood pressure.

00:57:59.140 | So you want to try to correlate any symptoms you're having

00:58:02.700 | with vital signs that you modify, right?

00:58:05.540 | So take your blood pressure if you're feeling faint.

00:58:08.220 | If it's low, one thing you can do easily is to hydrate.

00:58:12.540 | That was something else.

00:58:13.460 | I used to not drink much

00:58:14.700 | because I don't want to have to pee in the operating room.

00:58:18.040 | - I can imagine that'd be pretty uncomfortable.

00:58:19.420 | I don't want to be the patient that you're operating on

00:58:21.240 | when you have to go use the bathroom.

00:58:22.540 | - Yeah, so now, and then I'll reveal

00:58:25.300 | that I had a kidney stone, which is common among surgeons.

00:58:30.300 | This was a decade ago.

00:58:32.740 | And since then, I hydrate all the time.

00:58:37.100 | So I hydrate to the point

00:58:38.300 | that my urine is crystal clear all the time.

00:58:40.740 | - And that helps with some of the brain clarity.

00:58:43.300 | So interesting.

00:58:44.140 | I've done a little bit of work

00:58:44.960 | with people in the special operations community.

00:58:46.980 | And I think people hear about them and they think,

00:58:48.820 | oh, you know, what's the magic potion that they're taking?

00:58:51.380 | What are they doing?

00:58:52.220 | And they do a number of very interesting things.

00:58:55.160 | But one of them is they really emphasize hydration.

00:58:59.380 | They're just like hydration, water,

00:59:01.460 | sometimes water with electrolytes

00:59:02.760 | if they're working in hot conditions,

00:59:05.020 | but just hydration, hydration, hydration.

00:59:06.380 | - I was skeptical and I used to dehydrate.

00:59:09.700 | I felt better dehydrated and fit, you know,

00:59:12.020 | but as I've matured, I think it's very, very important.

00:59:17.020 | And for, you know, for your blood pressure,

00:59:20.580 | for your general health and for your kidneys.

00:59:24.420 | - Yeah, you mentioned sleep.

00:59:26.020 | Is there a relationship

00:59:26.900 | between sleep deprivation and stroke risk?

00:59:29.200 | - That's a great question.

00:59:31.980 | There's, interestingly,

00:59:34.140 | strokes occur more commonly during sleep.

00:59:37.680 | It's not known why.

00:59:40.260 | One theory is that it's related to circadian rhythms.

00:59:43.320 | I don't know if there's a relationship

00:59:46.700 | between sleep deprivation and stroke.

00:59:51.700 | - I'd like to take a brief break

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01:01:27.700 | I'm gonna tell a horror story,

01:01:29.440 | but not, I want to repeat, not to demonize chiropractors.

01:01:34.260 | Here's the positive story.

01:01:36.180 | I had a back thing, my back hurt,

01:01:39.540 | and I wasn't sure what I needed to do.

01:01:41.300 | And a chiropractor gave me some exercises to do

01:01:45.020 | that essentially were like the up-dog movement in yoga

01:01:48.700 | that my understanding is it helped the disc bulge

01:01:51.260 | kind of work its way back into the spinal column.

01:01:53.360 | And it worked terrifically well.

01:01:55.060 | I took no medication.

01:01:56.420 | I required no surgery.

01:01:58.100 | And I eventually learned to correct some imbalances

01:02:01.020 | that have led me to not have that issue again.

01:02:03.480 | It was really remarkable.

01:02:04.380 | And this chiropractor essentially saved me from surgery.

01:02:09.140 | And I'm forever grateful.

01:02:11.460 | So I think there are excellent chiropractors out there.

01:02:14.880 | But when I was a postdoc living in San Francisco,

01:02:18.180 | I had a roommate, I believe she was a neurology resident,

01:02:21.740 | and she came back from the clinic at UCSF.

01:02:24.020 | And she told me this story that a patient had come in

01:02:27.700 | who was experiencing some hemiparalysis of the face.

01:02:30.680 | That patient, I believe it was a young woman,

01:02:33.740 | had gone for a neck adjustment or head adjustment

01:02:36.540 | at a chiropractor.

01:02:37.380 | - She ended up with a dissection of her artery.

01:02:38.740 | - Right, and something had happened,

01:02:39.940 | and she had essentially a stroke.

01:02:42.260 | And so I share both these stories to make very clear

01:02:45.340 | that I have nothing against chiropractors,

01:02:47.900 | but I think like any health practitioners,

01:02:50.180 | they come in a range of talents.

01:02:51.780 | And this was really, like for me, an alarm.

01:02:57.060 | And I decided at that point,

01:02:58.380 | I would never allow a chiropractor to adjust my neck.

01:03:01.340 | I said, okay, you can make adjustments to my back,

01:03:03.540 | you can give me suggestions about exercises to do,

01:03:05.620 | but how common are these?

01:03:07.620 | You said it's a hemi-dissection?

01:03:11.100 | - It's a dissection of an artery,

01:03:13.100 | either the vertebral artery in the back

01:03:15.820 | or the carotid artery up closer in the front.

01:03:19.700 | - So no cutting when you say dissection,

01:03:21.260 | they're basically making an adjustment, yeah.

01:03:23.460 | - Well, what happens is, and I agree with,

01:03:26.260 | and we're on the same page.

01:03:27.620 | I recommend patients, if they're gonna have chiropractory,

01:03:30.900 | not to have manipulation of their neck,

01:03:33.340 | 'cause that's what occurs.

01:03:34.180 | It's not common, but I see it, we see it.

01:03:38.420 | What happens is the artery is damaged.

01:03:42.460 | The manipulation of moving the bone in the soft tissues

01:03:46.020 | causes a tear in the wall of the artery.

01:03:50.820 | And what occurs, interestingly,

01:03:53.460 | is that the blood that's usually in the space,

01:03:56.580 | the lumen, the middle of the artery,

01:03:59.180 | gets into the wall and causes a false lumen,

01:04:03.140 | a false passage, and that blood in the wall

01:04:07.780 | pushes part of the wall into the main artery,

01:04:11.500 | obstructing flow and sometimes causing a clot to form

01:04:16.500 | that can be dislodged and go up to the brain.

01:04:19.220 | - Yikes.

01:04:20.060 | So, and there's no way to know

01:04:22.540 | whether or not this is gonna happen.

01:04:24.220 | - No, that's why I recommend not having neck manipulation

01:04:28.860 | by a chiropractor.

01:04:30.100 | Even if it's rare, it's so devastating when it occurs

01:04:35.100 | that, personally, I would avoid that.

01:04:38.080 | - Yes, I tell the chiropractor,

01:04:42.420 | "Stay away from anything above the shoulders, please."

01:04:46.880 | And then the back work has been beneficial.

01:04:48.940 | Again, these exercises,

01:04:50.060 | perhaps the most beneficial thing about it.

01:04:52.560 | As long as we're there,

01:04:53.400 | I realize it's a bit of a niche condition,

01:04:54.980 | but what about hanging upside down?

01:04:56.400 | I had one of these inversion tables.

01:04:58.060 | I really enjoyed that thing.

01:04:59.460 | But then once I looked at my camera phone

01:05:01.300 | while I was hanging upside down,

01:05:02.260 | and it looked like I was gonna blow a gasket

01:05:04.140 | from all the vasculature in my forehead.

01:05:06.100 | Is it bad to hang upside down?

01:05:07.860 | - No evidence that it's bad.

01:05:09.700 | - Oh, good, oh, good.

01:05:10.820 | Maybe I'll get an inversion table again.

01:05:13.400 | As long as you don't stay there, of course.

01:05:14.940 | You got, okay, great.

01:05:18.420 | Would you let your kids play football or rugby?

01:05:21.420 | - That's a great question.

01:05:22.380 | I would not.

01:05:23.860 | That's my personal decision.

01:05:25.100 | I think there are a lot of benefits

01:05:26.620 | to children playing football, rugby, like any sport.

01:05:31.620 | It's a team sport.

01:05:32.980 | A lot of good skills are learned

01:05:34.780 | besides just the physicality of it, the coordination,

01:05:41.340 | but being a team player and the socialization.

01:05:44.540 | But I think, talking about tackle football,

01:05:48.420 | I think the risk, there is still risk.

01:05:52.980 | We're just learning about it.

01:05:54.260 | And even high school players

01:05:57.460 | who many years ago were found to have multiple concussions

01:06:02.460 | are showing up when they're doing autopsies

01:06:06.900 | with some of this chronic traumatic encephalopathy.

01:06:10.520 | I wanted to play football as a kid,

01:06:13.660 | and I'm not that big.

01:06:14.980 | I mean, I'm a big guy.

01:06:16.080 | And my parents didn't let me, which is fortunate

01:06:20.500 | because I'm sure I would have been put at risk for injuries,

01:06:25.500 | not just head injuries, other injuries.

01:06:29.300 | My son, who's a very good athlete,

01:06:31.660 | he played four years of high school baseball and soccer,

01:06:36.040 | was asked to try out for the quarterback position

01:06:38.940 | his senior year.

01:06:40.700 | And we went out to try out,

01:06:42.820 | and he decided, with my encouragement, not to play.

01:06:47.820 | - Did he go to Gunn High School?

01:06:49.660 | - Yeah, he went to Menlo.

01:06:50.960 | - Okay, I went to Gunn.

01:06:52.300 | Our football team was, at that time, was bad enough

01:06:54.860 | that there was no incentive to play.

01:06:56.680 | What about soccer and heading the ball?

01:06:58.320 | I've actually heard that can be problematic,

01:06:59.740 | which to me, at first, when I heard that,

01:07:01.300 | I was like, "Nah, there's no way."

01:07:02.780 | I mean, the ball is so light.

01:07:04.180 | But is there any evidence that repeated heading the ball?

01:07:06.260 | - There is.

01:07:07.200 | Again, it's not incontrovertible,

01:07:11.420 | but there is some evidence that multiple headings

01:07:15.260 | can cause some concussions and some long-term injury.

01:07:20.260 | Again, when I studied this in detail

01:07:24.140 | as a 49ers neurosurgeon back in the '90s,

01:07:29.980 | there was very little data,

01:07:31.740 | although there was some evidence even then

01:07:34.060 | that soccer players had a high incidence,

01:07:38.020 | particularly female soccer players

01:07:39.620 | had a high incident of concussion, surprisingly.

01:07:42.740 | But now there's much more evidence that head injuries

01:07:46.340 | and even heading the ball may lead to some injury.

01:07:50.460 | - I feel like if a sport is not your profession,

01:07:55.580 | the risk-benefit analysis is pretty clear.

01:07:59.380 | Like, why box?

01:08:01.940 | I understand it's a great sport.

01:08:03.140 | There's a lot to learn there.

01:08:05.060 | Done a little bit of it in the past,

01:08:06.420 | but unless you're gonna get paid

01:08:08.980 | substantial amounts of money,

01:08:10.380 | and maybe even then, it's probably not worth it.

01:08:13.020 | - Well, I feel the same way.

01:08:15.300 | It is different for professional athletes.

01:08:17.220 | I mean, this is their job.

01:08:18.700 | I remember talking with Steve Young at one point

01:08:23.060 | about continuing to play or finally deciding to retire.

01:08:27.140 | And I was thinking, what if I was asked

01:08:30.980 | to retire as a neurosurgeon at the prime of my career?

01:08:34.860 | It's your profession.

01:08:39.300 | It's your income.

01:08:40.420 | It's how you identify yourself.

01:08:43.660 | Your self-esteem is dependent on it.

01:08:48.100 | Your family maybe put pressure on you

01:08:50.540 | as a professional athlete.

01:08:52.060 | If you're not a professional athlete,

01:08:55.300 | I think for me, and this is my own opinion individually,

01:08:58.860 | I think there's less of a controversy,

01:09:02.580 | and there's so many other sports

01:09:05.620 | which benefit in the same way

01:09:09.620 | as football or boxing.

01:09:13.500 | Why not participate in those?

01:09:18.060 | That's my feeling, but I know it's a controversial subject.

01:09:21.820 | - Maybe we can circle back a little bit

01:09:23.180 | on a fairly common scenario.

01:09:27.060 | You're in the attic and you're looking for something,

01:09:29.300 | you stand up, boom, you hit your head on a beam

01:09:31.820 | and you're kind of dizzy for a bit.

01:09:33.380 | Or recently our podcast team was on tour in Australia

01:09:37.140 | and the way that the shelf over the kitchen sink

01:09:40.220 | in our Airbnb was arranged,

01:09:42.820 | it was certain that everyone pretty much

01:09:45.060 | would hit their head hard on that thing at some point.

01:09:48.340 | Does one need to worry about one kind of dizzy-inducing

01:09:52.140 | head hit from everyday life?

01:09:55.820 | I think a lot of people are kind of scared,

01:09:57.220 | like do they do brain damage

01:09:59.180 | or is the evolutionary adaptation,

01:10:01.980 | which is the thick skull,

01:10:03.580 | sufficient to keep us safe in most cases?

01:10:06.780 | - I don't think you need to worry in general,

01:10:08.660 | especially if your symptoms resolve

01:10:10.300 | within a relatively short period of time.

01:10:12.380 | - Such as how long, a day or two?

01:10:15.060 | - Yeah, I mean, even if you have a mild concussion

01:10:18.620 | and you recover within a day or two,

01:10:20.380 | I don't think there's any need to worry or get a scan.

01:10:24.300 | And it's a commonplace occurrence.

01:10:26.860 | - Yeah, I think your answer will set a lot of minds at ease

01:10:29.820 | because people do worry.

01:10:31.580 | I mean, there's something so mysterious

01:10:33.780 | about the stuff that occurs inside the cranial vault.

01:10:36.100 | We can't look to something, we can't take our pulse.

01:10:39.580 | It's so hard to know what's going on in there.

01:10:44.060 | - Well, as you say,

01:10:44.900 | that's why we develop very thick skulls

01:10:47.300 | to protect the most important organ.

01:10:49.700 | - Because after all the tissue doesn't regenerate,

01:10:52.920 | at least not much of it.

01:10:53.760 | There are a few areas where there are neurons

01:10:55.820 | that can replenish.

01:10:56.820 | - You know, I'm gonna take issue with you at that

01:11:00.460 | because the prior notion, of course,

01:11:03.380 | was that once nerve cells in the brain die,

01:11:06.760 | they don't regenerate.

01:11:08.440 | And for a long time it was thought

01:11:10.780 | you don't produce any new nerve cells,

01:11:13.340 | any new stem cells in the brain.

01:11:14.980 | And we used to think after an injury

01:11:19.340 | or a disease like a stroke,

01:11:22.620 | when that tissue was damaged and you were paralyzed

01:11:25.040 | or you couldn't talk, that there was no way to recover,

01:11:27.080 | that those circuits were dead.

01:11:29.300 | It turns out that is not true.

01:11:32.560 | And we are learning that, I think, in recent years.

01:11:36.320 | When I trained, there was no hope to restore function

01:11:40.320 | in patients who had a stroke, traumatic brain injury,

01:11:44.440 | spinal cord injury, and other diseases,

01:11:50.160 | ALS, Lou Gehrig's disease, Parkinson's disease.

01:11:54.020 | Now we are learning that there is hope.

01:11:58.900 | We know that stem cells do form in the adult brain.

01:12:03.180 | That's not controversial anymore.

01:12:06.140 | We know that other circuits can take over

01:12:08.660 | for circuits that were dead.

01:12:10.740 | And we know now, and this is some of the work

01:12:13.380 | that we're doing with chronic stroke patients

01:12:15.640 | who we thought could not recover after six months at all,

01:12:18.980 | we know that there are ways of promoting regeneration

01:12:23.980 | or recovery of function.

01:12:26.760 | We're still working out the details of that.

01:12:29.820 | But for instance, we've done studies,

01:12:33.220 | and this is still in clinical trial phase,

01:12:38.220 | with patients who are years out from a stroke,

01:12:41.700 | they've been through rehab,

01:12:43.180 | they've been through physical therapy,

01:12:46.680 | and 90% or more of recovery after a stroke

01:12:51.380 | occurs in the first six months.

01:12:52.780 | After that time, you know patients are not gonna recover.

01:12:56.060 | And now we are finding in some of our early trials

01:13:00.360 | with patients that if you, for instance,

01:13:03.420 | put in stem cells into the brain,

01:13:06.200 | or if you, another treatment which was approved by the FDA,

01:13:12.180 | the very first for chronic stroke,

01:13:13.900 | if you put a stimulator on the vagus nerve in the neck

01:13:17.460 | and stimulate, coupled with physical therapy,

01:13:22.460 | intensive physical therapy,

01:13:24.980 | you can improve arm function in those patients.

01:13:28.220 | In our patients that we've treated in multiple trials,

01:13:31.100 | we're seeing early indications that patients years out

01:13:35.220 | from a stroke can start to recover function in their arms,

01:13:40.220 | in their legs, in their speech.

01:13:43.040 | And we don't know all the mechanisms,

01:13:45.260 | but the old notion that these circuits are dead

01:13:48.140 | is simply not true.

01:13:49.980 | They can be resurrected.

01:13:52.180 | And so, you know, this is part of the excitement

01:13:56.060 | about discovery and doing research

01:14:00.180 | and trying to translate into the clinical arena.

01:14:03.140 | - Yeah, oftentimes this boils down

01:14:04.580 | to really critical of the moment decisions.

01:14:06.940 | I'll tell a story, I won't reveal the hospital

01:14:10.900 | or the exact players involved.

01:14:13.040 | But some years ago, an ex-girlfriend of mine,

01:14:16.820 | who then was just somebody I was friends with slash dating,

01:14:21.240 | contacted me and said that her dad had had a stroke.

01:14:25.480 | And I was near that hospital.

01:14:27.660 | So I went and spoke to the resident

01:14:31.680 | and the resident who was overseeing the case

01:14:33.960 | essentially said, look, it's hopeless.

01:14:35.560 | There's a huge necrotic piece of tissue in there.

01:14:38.860 | The probability of any kind of quality of life

01:14:41.240 | is essentially zero.

01:14:42.740 | My suggestion, and I was there

01:14:44.240 | as the resident made the suggestion,

01:14:46.800 | would be to remove him from life support, essentially.

01:14:50.960 | And the other members of the family were like,

01:14:53.120 | oh my goodness, right?

01:14:53.960 | This is not a situation anyone wants to be in.

01:14:56.720 | I made a couple of calls,

01:14:58.400 | including to someone who's previously been a guest

01:15:02.300 | on this podcast, who's highly qualified

01:15:04.880 | to know about this sort of thing.

01:15:05.980 | They asked a couple of questions

01:15:07.040 | about the location of the stroke,

01:15:08.960 | which side of the brain it was on,

01:15:10.460 | and said, keep him alive.

01:15:12.700 | There's a good chance that he'll have

01:15:14.880 | some degree of recovery of function.

01:15:16.760 | So that's what they did.

01:15:18.000 | And indeed, while he lost some motor abilities,

01:15:23.000 | lost some speech abilities,

01:15:24.200 | and has some disruption of affect,

01:15:26.140 | where he'll sort of spontaneously laugh or cry

01:15:28.200 | from time to time, he has, at least by my observation,

01:15:31.400 | been able to enjoy substantial amounts of life,

01:15:34.320 | interacting with grandkids, enjoying holidays,

01:15:36.840 | and actually took, I was told,

01:15:38.320 | some physical steps at some point,

01:15:41.400 | with assistance, with a walker.

01:15:42.720 | He's done a lot of physical rehab.

01:15:45.240 | Obviously, a really hard situation,

01:15:47.480 | but it told me that oftentimes,

01:15:50.440 | when we think that all is lost, not all is lost,

01:15:54.480 | even in people in their 70s.

01:15:56.960 | - Right, it has to do with plasticity.

01:15:59.860 | And we all wish we were neonates or infants,

01:16:04.380 | because the body, including the brain, is so plastic.

01:16:08.040 | That's the ability to regenerate tissue

01:16:10.840 | and circuits and recover.

01:16:12.480 | So if an infant has a stroke and is paralyzed on one side,

01:16:17.480 | usually they can make an excellent,

01:16:19.880 | if not complete, recovery.

01:16:21.400 | - This is the, as I recall from my undergraduate years,

01:16:24.740 | the Kennard principle.

01:16:25.980 | If you're gonna have a brain injury,

01:16:27.100 | have it early in life.

01:16:28.040 | - Exactly.

01:16:28.880 | So, I mean, you notice this too.

01:16:30.760 | When I cut myself now, it can take a week

01:16:34.740 | for that cut to heal.

01:16:35.900 | When my granddaughter, who's six years old,

01:16:38.500 | cuts herself the next day, it's totally healed.

01:16:40.540 | - So little kids are like salamanders, right?

01:16:42.780 | They almost, by the way, that was a biology joke.

01:16:45.740 | They're not like salamanders.

01:16:47.260 | But salamanders can regenerate entire limbs

01:16:50.900 | by the maintenance of a small stem cell population

01:16:52.980 | at the tip of the limb bud, or what would be the limb bud.

01:16:58.060 | And it is remarkable how kids can regenerate without a scar.

01:17:02.480 | They can oftentimes, they can't grow an entire hand back,

01:17:05.000 | but it's kind of striking how much plasticity there is.

01:17:07.240 | - And that's what we're trying to develop,

01:17:09.040 | are new ways of promoting plasticity

01:17:11.960 | in the adult brain, as an example.

01:17:13.760 | So we think stem cells injected through various mechanisms,

01:17:18.760 | stimulation of the brain, or the vagal nerve, as an example,

01:17:24.120 | can promote plasticity.

01:17:26.720 | In a sense, we think what's happening

01:17:28.980 | is that these methods can turn the adult brain

01:17:33.940 | into an infant brain, in some ways.

01:17:36.500 | - Where are the stem cells coming from in these experiments?

01:17:39.140 | - It depends.

01:17:40.340 | There are different sources.

01:17:41.500 | So some of the studies I've done previously

01:17:45.440 | with other companies, they made the stem cells

01:17:49.460 | either from bone marrow donors, so they were mesenchymal,

01:17:55.520 | or another group made the cells from fetal neural tissue.

01:18:00.520 | - Okay, so just to orient people,

01:18:04.820 | inside the bone, you have the marrow.

01:18:06.780 | Most people know that because they've ordered it

01:18:08.980 | at a restaurant, cow marrow, that is, typically.

01:18:13.980 | The cells within the marrow contain, as I recall,

01:18:18.100 | a hemopoietic population.

01:18:20.180 | So a population of sort of potential blood cells,

01:18:24.300 | cells that can become blood cells, or other things.

01:18:26.420 | And if taken out, put into a Petri dish,

01:18:28.720 | and given the appropriate factors,

01:18:31.320 | you can drive the fate of those stem cells

01:18:33.680 | to be, say, neurons, or cardiac cells.

01:18:36.720 | And then you're taking those cells

01:18:38.280 | and you're injecting them into the brains of patients

01:18:41.120 | in the hopes that they will become neural cells,

01:18:45.060 | neurons that will incorporate into the circuitry.

01:18:47.080 | - Actually, that was the initial notion 20 years ago

01:18:49.760 | when we started doing this,

01:18:50.880 | was that these cells you put in become,

01:18:55.560 | these exogenous cells you inject,

01:18:58.100 | become neurons, and astrocytes, and oligodendrocytes,

01:19:01.320 | all the cells in the brain,

01:19:02.640 | and that the neurons reconstitute circuits.

01:19:05.360 | That is not how they work.

01:19:08.320 | The way they work, and this is why it may not matter

01:19:12.800 | what particular type of stem cell you put in,

01:19:15.340 | the way they work, primarily,

01:19:18.040 | is by secreting very powerful proteins, molecules,

01:19:22.960 | growth factors that promote native recovery.

01:19:26.800 | So they promote angiogenesis,

01:19:30.200 | they promote native neurogenesis,

01:19:32.520 | endogenous gliogenesis, synaptogenesis,

01:19:36.040 | but the main benefit may be

01:19:38.100 | that they modulate the immune system.

01:19:40.060 | That's what we're finding.

01:19:41.620 | So by modulating, somehow, the immune system in the brain,

01:19:46.280 | they are able to induce plasticity and recover function.

01:19:50.240 | - Interesting.

01:19:51.120 | I'm tempted here to weave in the stories

01:19:53.660 | that date back to the '90s,

01:19:54.960 | but that we see more and more of,

01:19:56.280 | mostly studies in rodents, but a few in humans,

01:19:58.540 | showing that there are dormant stem cell populations

01:20:02.040 | in certain compartments of the brain,

01:20:03.440 | the dentate gyrus, or the hippocampus,

01:20:05.040 | the olfactory bulb, et cetera,

01:20:06.960 | that upon hyperoxygenation,

01:20:11.060 | or increasing blood flow to the brain,

01:20:14.220 | largely by virtue of exercise,

01:20:16.660 | but also sometimes by way of engaging

01:20:18.540 | in learning tasks and exercise,

01:20:20.780 | that you can basically cause the release of stem cells

01:20:23.340 | that normally would lie dormant.

01:20:25.260 | Is that literature reason enough

01:20:28.660 | to suggest that people who've had a stroke

01:20:31.780 | continue to move their body, to walk, get exercise,

01:20:34.920 | maybe do resistance training,

01:20:36.020 | maybe even some skill-related training?

01:20:37.940 | - Yes, there's a lot of evidence that activity,

01:20:41.940 | physical therapy, even forced activity,

01:20:45.500 | is very beneficial.

01:20:46.700 | And it's not just stimulating endogenous stem cells

01:20:51.260 | in the brain, but it's multiple mechanisms.

01:20:54.380 | It's recruiting circuits that were not involved before.

01:20:58.640 | For instance, studies have been done on stroke patients

01:21:02.420 | who make a recovery show that

01:21:05.780 | not only is the side of the stroke improving in some cases,

01:21:10.420 | but the other side of the brain

01:21:13.140 | is showing increased activity.

01:21:15.900 | So circuits on the other side of the brain

01:21:18.540 | may be contributing to the recovery

01:21:20.540 | on the side of the stroke brain.

01:21:24.160 | So it's much more complex than we thought it was.

01:21:27.500 | - Years ago, I developed an affection for a literature.

01:21:31.940 | It wasn't a very prominent literature,

01:21:34.400 | but I found it really interesting,

01:21:36.440 | is the work of a guy named Timothy Schallert

01:21:38.820 | and Teresa Jones.

01:21:40.580 | - I know both of them. - Are you familiar with this?

01:21:42.060 | - Yeah, we almost recruited Tim to our department.

01:21:44.700 | - Yeah, the sort of overarching theme of this literature

01:21:47.300 | was it was animal work,

01:21:49.260 | but I think some of it might've been translated to humans,

01:21:51.380 | which was that, for instance,

01:21:52.740 | if somebody has damage on one side of the brain,

01:21:55.260 | because of the way the circuits are organized,

01:21:57.180 | and of course, you know this better than anyone, Gary,

01:21:59.540 | but that one might experience deficits in limb movement

01:22:02.300 | on the opposite side.

01:22:03.940 | And that the tendency for somebody like that

01:22:06.740 | is to then over rely on the intact limbs,

01:22:09.740 | essentially lean on the intact limbs.

01:22:13.860 | And the approach that they took

01:22:15.660 | to try and recover function was really interesting.

01:22:19.340 | They had these animals,

01:22:21.640 | and I think eventually there was some human work done,

01:22:23.740 | I could be mistaken,

01:22:25.420 | sort of tie up the more active uninjured arm or leg or hand,

01:22:30.420 | such that they then had to rely on the non-dominant,

01:22:34.860 | or let's just call it injured,

01:22:36.440 | sometimes even flaccid paralysis limb.

01:22:38.660 | And in that way, they could generate a lot of plasticity

01:22:42.020 | that normally would escape the patient,

01:22:43.940 | especially in the days and weeks following the injury.

01:22:46.420 | Just forcing movement,

01:22:48.620 | or forcing the attempt to move of the injured pathway.

01:22:52.220 | I find this literature to be so striking,

01:22:54.340 | and maybe one that should deserve more attention.

01:22:57.100 | - Yeah, it's called constraint therapy.

01:22:59.100 | And not only has it been shown

01:23:01.140 | in animal studies preclinically,

01:23:03.440 | but it's been shown in some clinical studies

01:23:07.440 | of patients with stroke.

01:23:09.180 | In fact, one of the trials we did

01:23:11.000 | with transplanting stem cells into the brain

01:23:14.320 | included restraining the good limb

01:23:17.880 | to force use of the other limb.

01:23:20.400 | So there's some very intriguing data

01:23:23.600 | suggesting that that's important.

01:23:25.040 | However, some of the animal studies also suggest

01:23:30.040 | that you may have to wait a time.

01:23:32.280 | If you force use of the involved limb too soon,

01:23:36.980 | it can be detrimental to the recovery.

01:23:38.900 | - I see.

01:23:39.740 | - So there may be an important temporal factor there

01:23:43.340 | in terms of the timing of when you do that.

01:23:46.060 | - Is there anything that people can do or take

01:23:50.180 | for neuroprotection after an injury

01:23:53.020 | to essentially try and rescue neurons

01:23:55.460 | that would otherwise die?

01:23:56.460 | - Right, so this is a very interesting subject.

01:23:59.660 | Back in the late 1980s, 1990s,

01:24:04.340 | a lot of emphasis was placed on trying

01:24:07.480 | to protect the brain against acute stroke.

01:24:10.860 | Different pharmacologic agents were tried.

01:24:13.400 | Probably a thousand different drugs were tried

01:24:19.640 | which blocked the pathway leading to cell death.

01:24:25.200 | So interestingly, when you deprive the brain

01:24:29.160 | and the neurons of oxygen and glucose,

01:24:31.340 | they don't die immediately and it takes some time

01:24:35.680 | and it's actually an active process.

01:24:37.880 | So the release of these excitatory amino acids occurs.

01:24:42.880 | So normally, as you know, glutamate, aspartate

01:24:47.760 | are important neurotransmitters in the brain

01:24:49.720 | and you need them to function.

01:24:51.900 | But after a stroke, when there's a deprivation

01:24:54.560 | of oxygen and glucose and a mismatch

01:24:57.340 | between the metabolism and the supply

01:25:00.600 | of oxygen and glucose, for some reason there's a release

01:25:05.160 | of these excitatory amino acids like glutamate

01:25:09.520 | and that causes an influx of calcium into the neurons

01:25:14.460 | which is the final common pathway to dying.

01:25:17.320 | And then there are other pathways that can then lead

01:25:21.720 | to release of free radicals which are more damaging

01:25:26.760 | and those can cause another type of cell death

01:25:28.960 | called apoptotic cell death.

01:25:30.520 | That's a cell death that occurs and requires protein synthesis

01:25:35.520 | and then with reperfusion, say the artery opens up,

01:25:41.000 | then you got a lot of inflammation.

01:25:42.740 | So these pharmacological treatments, as I say,

01:25:45.400 | a thousand of them were tried and they were found

01:25:49.000 | to be very effective in preclinical stroke models.

01:25:52.240 | So we could cure stroke in the lab.

01:25:55.420 | My lab studied this for probably 15 years

01:25:59.000 | and there was no doubt we could cure stroke

01:26:02.560 | if we got the drugs on board even after the stroke

01:26:05.640 | within a few hours, but it never was able to be translated

01:26:11.560 | to the clinical arena except for one case.

01:26:15.340 | So besides drugs that were tried,

01:26:17.920 | another method of protecting the brain was tried

01:26:21.800 | called mild hypothermia and that was a process

01:26:26.800 | of reducing the brain temperature and body temperature

01:26:31.700 | just a few degrees from 37 degrees centigrade to 33.

01:26:36.700 | And we were one of the first to show

01:26:39.900 | that that was protective even after the stroke in animals.

01:26:45.020 | - My understanding is that when you cool neural tissue,

01:26:48.220 | you quiet its electrical activity.

01:26:50.300 | In fact, this is a common tool for experimentation

01:26:54.140 | in neuroscience laboratories.

01:26:55.800 | You want to shut down a brain area transiently,

01:26:58.980 | you cool it down.

01:27:00.780 | - Right, and in fact, deep hypothermia has a profound effect

01:27:05.500 | on shutting down the metabolism.

01:27:07.000 | So that's why when someone, particularly kids,

01:27:10.440 | fall into a frozen pond with ice cold water,

01:27:14.400 | they can survive there for half an hour

01:27:18.200 | and make a complete recovery because their body temperature

01:27:21.640 | is dropped down to very low, like 20 degrees centigrade.

01:27:25.440 | But this is less, this is just a few degrees.

01:27:27.820 | So the amount, there is a slight decrease

01:27:30.800 | in the metabolic activity,

01:27:32.480 | but that does not account for all the protection.

01:27:34.420 | It's due to the fact that hypothermia, mild hypothermia,

01:27:38.900 | blocks many of those detrimental pathways.

01:27:41.360 | It blocks partly the release of those excitatory amino acids,

01:27:45.520 | glutamate, it blocks the calcium influx,

01:27:48.360 | it blocks the inflammation.

01:27:50.180 | And so that's probably why it works so well.

01:27:55.040 | It even blocks that other pathway of programmed cell death

01:27:58.440 | because it hits all these pathways.

01:28:01.520 | It's multifactorial, it's very effective.

01:28:04.200 | And in fact, it was finally shown in the early 2000s

01:28:09.200 | in prospective randomized studies that one type of stroke,

01:28:14.360 | actually two types, I should say,

01:28:16.400 | two types of stroke are benefited

01:28:19.760 | by cooling the brain quickly.

01:28:21.200 | One is cardiac arrest from ventricular fibrillation

01:28:25.040 | and prospective studies which were published in 2002

01:28:28.880 | showed that if you cool patients who have cardiac arrest

01:28:33.560 | and then are resuscitated out in the field

01:28:35.840 | down to between 32 and 34 degrees centigrade from 37,

01:28:40.600 | much better outcomes neurologically.

01:28:44.320 | That's from global ischemia.

01:28:45.920 | That's the no blood getting to the brain briefly.

01:28:49.120 | And the other area where it's been shown

01:28:50.920 | to have better outcomes is in neonatal,

01:28:55.580 | what's called hypostatic ischemic injury.

01:28:57.560 | Those are neonates who have lack of blood flow

01:29:00.240 | for some reason to the brain when they're born.

01:29:03.340 | And if you cool them, it's been shown in studies

01:29:06.200 | up to 10 years later

01:29:08.820 | that they have better cognitive outcomes.

01:29:11.840 | So for cardiac arrest in the mid 2000s,

01:29:16.840 | I think it was 2003,

01:29:19.920 | the American Heart Association determined

01:29:23.980 | it was a standard of care, a guideline

01:29:26.560 | that you had to cool patients after cardiac arrest.

01:29:30.560 | Yes.

01:29:31.400 | - How was the cooling done in the experiments

01:29:34.000 | that you were involved in?

01:29:35.500 | - Yeah, so there are many ways to do it,

01:29:37.660 | but in the animal models,

01:29:38.920 | you can just cool them with a cooling blanket, actually.

01:29:42.000 | In people, we got very interested in this.

01:29:45.000 | In fact, when I saw in the laboratory

01:29:47.320 | that it was so effective and that we could cure mouse

01:29:51.240 | and rat stroke by cooling,

01:29:54.200 | I started cooling my patients in the operating room

01:29:58.400 | because I felt, even if it hadn't been proven in patients,

01:30:04.200 | that it was so effective.

01:30:06.480 | It's the gold standard now, actually,

01:30:08.040 | for neuroprotection against stroke in the laboratory.

01:30:13.040 | So back in the 1990s,

01:30:17.080 | I started cooling all of my patients.

01:30:20.140 | We started by cooling them by packing them in ice

01:30:24.980 | and putting alcohol on them,

01:30:26.960 | but the operating room staff, appropriately,

01:30:30.440 | didn't like that 'cause alcohol's inflammable.

01:30:33.880 | So then we started using cooling blankets,

01:30:36.800 | and then a number of companies

01:30:38.320 | started developing cooling catheters,

01:30:42.520 | and I worked with several of these.

01:30:43.960 | So you can actually cool very quickly

01:30:46.960 | if you put a catheter into a vessel, say, in the groin,

01:30:51.960 | and infuse cold saline,

01:30:57.720 | which doesn't get into the circulation,

01:30:59.960 | but it cools the blood,

01:31:02.000 | and the cooled blood then circulates.

01:31:04.560 | Other ways of cooling are putting on special devices

01:31:09.120 | which cool quickly,

01:31:10.440 | and that's what's used now are external devices.

01:31:13.720 | People are working on cooling just the head with helmets.

01:31:16.780 | So it's still an active field of investigation for stroke

01:31:22.820 | and also for cardiac arrest, actually.

01:31:25.720 | It has not been proven in well-designed prospective trials

01:31:30.080 | that it works for garden-variety focal stroke.

01:31:34.600 | It works for cardiac arrest

01:31:36.080 | where there's global lack of blood flow to the brain,

01:31:38.760 | like when the heart stops.

01:31:40.160 | It hasn't been proven yet for the kind of stroke

01:31:44.360 | we've been talking about

01:31:45.240 | where there's a single-blocked artery to the brain.

01:31:48.040 | - So interesting.

01:31:48.880 | I mean, a lot of times on this podcast,

01:31:50.220 | we talk about the critical need for body temperature

01:31:52.540 | to drop by one to three degrees to get into deep sleep.

01:31:55.520 | We had Craig Heller,

01:31:56.920 | our colleague from the biology department at Stanford,

01:31:59.440 | on the podcast where he talked

01:32:00.520 | about some of the Palmer cooling,

01:32:01.960 | and essentially cooling the soles of the feet,

01:32:05.360 | the palms of the hands, and the upper part of the face

01:32:07.300 | as a way to more rapidly reduce core body temperature.

01:32:10.260 | I think these are fascinating areas for exploration

01:32:14.280 | that obviously have clinical applications,

01:32:18.860 | but also you'd imagine for some of the things

01:32:20.840 | we were talking about before,

01:32:21.940 | like just to provide a bit of neuroprotection

01:32:25.740 | after a head hit or provide a bit of neuroprotection,

01:32:28.640 | perhaps even as it relates to aging,

01:32:31.360 | spending a little bit of time, maybe 10 minutes a day,

01:32:34.460 | not badly hypothermic, please people,

01:32:37.840 | but slightly hypothermic,

01:32:39.240 | and then bringing the body temperature back up.

01:32:41.200 | - Yeah, I mean, I wouldn't recommend

01:32:42.720 | if you have a head injury or a TIA

01:32:46.200 | to stick your head in a snowbank,

01:32:49.280 | but even with traumatic brain injury,

01:32:52.160 | severe, not just concussion,

01:32:53.680 | but severe TBI, traumatic brain injury,

01:32:56.960 | studies were done looking at cooling hypothermia,

01:32:59.920 | and it's called mild hypothermia

01:33:01.560 | 'cause it's just a few degrees,

01:33:03.520 | and the studies were very suggestive,

01:33:05.520 | but didn't get to the point that it was proven,

01:33:09.800 | although certain subgroups who were cooled quickly

01:33:12.960 | seemed to do better.

01:33:14.520 | So I think it's a subject that's still being studied,

01:33:17.960 | and as I say, it's easy for us to do in the operating room.

01:33:21.680 | You don't wanna cool too much

01:33:22.840 | 'cause that can then interfere

01:33:24.640 | with other metabolic functions and clotting parameters,

01:33:29.440 | and it can cause increased infection

01:33:32.560 | if you go too low for too long,

01:33:34.040 | but I still let my patients cool just a few degrees,

01:33:39.040 | and we've had some anecdotal cases

01:33:42.520 | where patients have had problems,

01:33:46.560 | and because we cooled them, we think it made a benefit.

01:33:50.800 | For instance, we had one patient

01:33:52.960 | who we hadn't even done,

01:33:55.120 | I was getting ready to do a bypass

01:33:57.600 | to sew a scalp artery to a brain artery,

01:34:00.360 | but we hadn't even, I think, made the skin incision,

01:34:05.360 | and the patient had a cardiac arrest,

01:34:09.320 | and it lasted for a long time,

01:34:15.280 | so we were pumping on the chest, couldn't restore function,

01:34:19.360 | and it was way outside the amount of time

01:34:23.760 | that you would have expected a good recovery,

01:34:25.480 | but the patient had been cooled down to 33 degrees

01:34:29.000 | before we, by the time it had happened,

01:34:31.840 | and then we finally got the heart started.

01:34:35.360 | We ended up putting some,

01:34:36.960 | restoring flow through catheters and a heart-lung machine,

01:34:40.760 | and remarkably, the guy made a complete recovery.

01:34:43.400 | So anecdotal, but cases like that

01:34:47.760 | suggest maybe cooling even a few degrees

01:34:51.860 | has a protective effect on the brain.

01:34:54.200 | We certainly know it's true

01:34:56.000 | for cardiac arrest and global ischemia.

01:34:58.280 | - What are your thoughts on platelet-rich plasma, PRP?

01:35:02.520 | These days, we hear so much about PRP,

01:35:04.240 | I think it's FDA-approved for certain things, right?

01:35:07.080 | People will get blood drawn,

01:35:09.480 | they'll spin down platelets,

01:35:11.680 | and then put in platelet-rich plasma.

01:35:16.000 | A few years ago, people were making claims out there

01:35:18.320 | about PRP containing stem cells.

01:35:20.520 | Just for the record, my understanding,

01:35:22.760 | I'm sure someone will argue with me online, they always do,

01:35:24.880 | but my understanding is that PRP contains very few,

01:35:29.000 | if any, stem cells,

01:35:30.720 | and that it's not legal to assert

01:35:33.480 | that PRP is stem cell therapy,

01:35:35.500 | but PRP seems to be something that,

01:35:38.060 | after an injury or in anticipation of a surgery,

01:35:40.840 | people are starting to do more and more

01:35:42.280 | because they can go drop a few thousand dollars,

01:35:45.080 | and, I don't know, get this infusion of PRP.

01:35:47.800 | Does it work to help recover brain tissue

01:35:51.200 | or preserve brain tissue?

01:35:52.320 | Is there any evidence of that whatsoever?

01:35:54.080 | - I'm not an expert on platelet-rich plasma,

01:35:57.080 | but my reading of the literature

01:36:03.680 | cursorily suggests there's not hard evidence

01:36:08.160 | that it's beneficial.

01:36:10.080 | I think one has to be a little careful.

01:36:11.680 | For instance, I still get emails

01:36:16.400 | every few weeks from people saying,

01:36:20.440 | I've had a stroke or I've had a head injury,

01:36:24.020 | and should I go to Russia or India or Mexico

01:36:29.020 | and get stem cell therapy?

01:36:33.360 | - Yeah, this is a big topic area, yeah.

01:36:35.880 | - And you may have discussed it on another podcast.

01:36:38.040 | - I have not.

01:36:38.880 | I'll do a solo episode on stem cells

01:36:40.520 | and what they are and what they aren't.

01:36:41.960 | I just will, just, sorry to interrupt,

01:36:44.280 | but I'm aware of a clinic in Florida

01:36:46.960 | that was injecting stem cells into the eyes of patients

01:36:49.420 | with macular degeneration and some other eye issues,

01:36:52.000 | and those patients rapidly went blind.

01:36:53.960 | - Yeah, I was going to bring that up too.

01:36:54.800 | - Yeah, and that's what led the FDA

01:36:56.120 | to really clamp down on stem cell clinics in the U.S.

01:36:58.840 | - Although they haven't clamped down

01:37:00.080 | on those type clinics as well as they should.

01:37:02.160 | But I tell patients, no, if you go out of the country,

01:37:07.160 | often you don't know what you're getting.

01:37:09.240 | If there's not an equivalent of an FDA,

01:37:11.680 | which is overseeing it,

01:37:12.940 | you don't know whether these cell,

01:37:16.440 | where they come from sometimes.

01:37:18.140 | They're not published literature.

01:37:19.840 | You don't know where they're derived.

01:37:22.880 | We've seen cases of patients going elsewhere,

01:37:25.520 | getting injections into the brain or the spinal cord

01:37:28.160 | and developing tumors or other problems.

01:37:30.680 | So I discourage that, and I was going to bring up,

01:37:33.440 | even in this country, these clinics,

01:37:37.000 | and that was published a number of years ago,

01:37:40.060 | that clinic in Florida.

01:37:41.560 | Those patients had macular degeneration

01:37:45.960 | and they were losing their sight,

01:37:47.280 | but they could still see to some extent.

01:37:49.800 | They had their own adipose tissue taken.

01:37:53.640 | They sorted it for certain stem cells,

01:37:57.800 | mesenchymal stem cells,

01:37:59.200 | and it was re-injected into the eye.

01:38:01.840 | Should have been safe, right?

01:38:02.840 | Their own cells even.

01:38:04.320 | And as you say, several of them went blind.

01:38:07.200 | Irreversibly.

01:38:08.360 | Irreversibly.

01:38:09.280 | So I think this is very important

01:38:12.080 | to highlight the dangers of stem cell therapy in general.

01:38:15.940 | There's a lot of hope for it.

01:38:17.400 | I mean, we're engaged.

01:38:18.320 | We're just finishing a trial,

01:38:20.360 | a first in human trial at Stanford

01:38:22.840 | using cells we developed in my lab 20 years ago.

01:38:25.480 | It took us 20 years to prove that they were safe,

01:38:28.680 | effective, didn't cause tumors.

01:38:31.200 | And the study is looking very promising.

01:38:33.620 | It's a phase one study

01:38:34.800 | and we're making plans to do a phase two study

01:38:38.060 | with control patients, which you always want to do.

01:38:41.400 | But despite the hope, there is still a lot of hype.

01:38:46.400 | And I think it's very important to be careful

01:38:49.800 | about getting therapies that are not proven.

01:38:52.880 | - Yeah, and while we wouldn't want anyone

01:38:55.080 | to take any kind of unnecessary risk,

01:38:58.060 | you know, to me anyway,

01:38:59.320 | this goes back to the beginning of our conversation,

01:39:01.920 | that there's something very different about a knee

01:39:03.840 | from the brain, right?

01:39:05.200 | I'm not saying go get stem cells injected into your knee,

01:39:07.660 | but should you be the sort of person that wants to do that

01:39:10.960 | because you feel that's within your rights?

01:39:12.880 | You know, again, I don't tell people what to do.

01:39:14.440 | And you go to a clinic, they get stem cells,

01:39:17.500 | or I don't know, they take stem cells from some source

01:39:20.600 | and put them into your knee.

01:39:21.640 | I mean, that's a very different situation

01:39:24.440 | than injecting into the brain or spinal cord.

01:39:26.840 | - Some of the approaches to treat diseases of the brain

01:39:30.320 | or injuries to the brain are not injecting directly

01:39:33.240 | into the brain.

01:39:34.080 | They're injecting intravenously or intra-arterial,

01:39:37.680 | threading a catheter up, as we discussed,

01:39:39.440 | and injecting in the brain.

01:39:41.740 | Those cells, it turns out, don't even get into the brain.

01:39:45.400 | And the idea is that in some of the better studies

01:39:49.040 | that have been done in animals,

01:39:51.160 | that they work by modulating the immune system systemically.

01:39:55.420 | Those cells get trapped in the lung and the spleen,

01:39:59.060 | which people describe as bioreactors,

01:40:02.280 | and modulate the immune system,

01:40:03.920 | which does make some sense.

01:40:05.360 | As I say, we think one of the main benefits

01:40:08.760 | of these stem cells is that they modulate the immune system,

01:40:13.680 | and that helps with plasticity in the brain.

01:40:16.000 | But even intravenous delivery can be dangerous to the brain.

01:40:21.000 | - Yeah, this is an area that we will spend a lot more time

01:40:25.880 | on during this podcast.

01:40:27.300 | But despite what you just said,

01:40:30.560 | I think the data I've seen from your laboratory,

01:40:33.200 | and as you told me, there's a trial that's finishing up now

01:40:36.200 | that features those data,

01:40:39.240 | or that is where those data arrive from, rather,

01:40:42.520 | are really impressive.

01:40:43.640 | I mean, some people who were largely immobile or aphasic,

01:40:48.080 | they couldn't speak,

01:40:49.760 | in some cases are able to speak or move.

01:40:52.280 | And that's really remarkable.

01:40:53.360 | It's really exciting.

01:40:54.180 | So I think that the future of stem cells

01:40:56.240 | and stroke therapy is pretty bright,

01:41:00.760 | at least from where I sit.

01:41:02.320 | - Yeah, we don't want to oversell this,

01:41:04.880 | but some of the results in certain patients are remarkable.

01:41:09.720 | I mean, the patients and their families

01:41:12.280 | say it's changed their lives.

01:41:13.840 | If you see them before and after,

01:41:15.560 | it's almost like a miracle.

01:41:17.280 | Others are not as impressive,

01:41:18.960 | but so far in our trial,

01:41:22.680 | and we've treated 17 of the 18 intended patients,

01:41:27.320 | almost all the patients have recovered to some extent,

01:41:32.280 | and many of them have improved in a meaningful way

01:41:37.280 | if you use certain scales.

01:41:39.000 | So again, we want to be cautious.

01:41:41.440 | We're going to do a prospective randomized

01:41:43.920 | blinded controlled study,

01:41:45.920 | and that's the way it should be done.

01:41:47.840 | And if that's positive,

01:41:50.040 | it would lead to a phase three larger study,

01:41:55.040 | again, blinded controlled.

01:41:57.640 | And if that's positive,

01:41:58.920 | then it would lead to commercialization, FDA approval.

01:42:02.880 | It's a long process.

01:42:04.440 | I've spent 23 years

01:42:08.000 | and more than $46 million in grants and philanthropy

01:42:13.000 | getting it to this stage.

01:42:16.200 | - Wow. - Yeah.

01:42:17.400 | - Wow.

01:42:18.760 | That's a lot of time and a lot of money.

01:42:21.780 | Amazing.

01:42:22.880 | - That's the way science

01:42:24.160 | and translation to clinical medicine is.

01:42:27.200 | - I would be remiss if I didn't ask,

01:42:31.040 | what are some of the things

01:42:32.240 | that you think could accelerate that process,

01:42:34.280 | or is that just the slow iterative process

01:42:36.320 | that is science and medicine?

01:42:37.400 | I mean, for instance,

01:42:38.460 | if there was five times as much money,

01:42:41.640 | would the science progress at five times the rate?

01:42:44.900 | Probably not.

01:42:46.280 | - No, but money is a factor.

01:42:48.840 | It's not the only factor.

01:42:50.800 | The FDA is appropriately very cautious.

01:42:55.800 | I think other countries,

01:42:57.960 | the equivalent of the FDA

01:42:59.920 | moves things along a little quicker,

01:43:01.440 | especially for therapies where there's no other treatment.

01:43:04.960 | So I think those factors are important

01:43:11.400 | and would accelerate it.

01:43:12.920 | I think greater collaboration with industry

01:43:15.580 | and promoting more academic industry

01:43:17.840 | kinds of relationships would help

01:43:20.880 | because the government agencies

01:43:25.520 | do not provide enough money to do the final stage.

01:43:29.680 | You know, there's called this valley of death

01:43:32.400 | where you get initial encouraging data, even clinically,

01:43:37.400 | but you can't move the hurdle to get it into FDA approval

01:43:43.360 | because of money in some cases.

01:43:46.900 | I've seen, as an example,

01:43:49.080 | a number of very good stem cell therapies

01:43:52.420 | not make it because the companies went bankrupt.

01:43:56.100 | The board of directors of the company felt

01:43:58.820 | the results were good, but not good enough,

01:44:00.620 | and they pulled the funding.

01:44:02.660 | So this is a whole area which I was not well informed of

01:44:07.540 | until I got into this of how you move through the FDA

01:44:12.100 | and how you work with industry.

01:44:15.760 | I haven't formed a company yet, but I'm gonna have to

01:44:20.580 | because for the next trial,

01:44:22.060 | this trial I was fortunate to get a grant

01:44:24.940 | from CIRM, California Institute for Regenerative Medicine,

01:44:27.660 | of $12 million.

01:44:28.500 | - So that's taxpayer dollars.

01:44:30.040 | - Exactly.

01:44:30.880 | - Great use of taxpayer money,

01:44:31.820 | putting it to really forward-thinking research.

01:44:34.440 | - But the next trial, and our results are good enough

01:44:38.460 | that we probably will only need,

01:44:40.260 | if we do a statistical power analysis, 69 patients.

01:44:44.540 | Initially, we thought we'd need 170 patients,

01:44:47.060 | but the results keep getting better and better.

01:44:49.300 | So now, it seems we would only need about 69 patients.

01:44:54.300 | That will cost at least 45 million,

01:44:59.520 | and as the trials get larger, even more.

01:45:03.180 | So yeah, we need to figure out a better way

01:45:06.280 | to allocate money to make these advances.

01:45:09.980 | - It sounds like a company or some role of industry

01:45:13.020 | is going to be necessary.

01:45:14.980 | - Well, you might be interested in investing, right?

01:45:17.380 | - Well, this podcast is always available free

01:45:22.460 | at a standard Huberman Lab podcast.

01:45:23.860 | Our premium channel actually generates money.

01:45:27.340 | We do Ask Me Anythings and things of that sort.

01:45:29.560 | We have donors that have come in for a dollar match,

01:45:31.400 | and we do philanthropy to laboratories

01:45:33.340 | at Stanford, Salk Institute, Columbia University.

01:45:35.820 | We've already done that.

01:45:36.660 | We're gonna do more of this.

01:45:37.860 | - Well, I was being facetious.

01:45:39.540 | - Oh, no, listen, we could explore it.

01:45:41.280 | One of the guidelines is that we fund research

01:45:44.200 | on humans exclusively, so we could talk about that.

01:45:48.420 | The former colleague of ours at Stanford

01:45:51.900 | once told me the joke.

01:45:54.620 | We'll see if I get in trouble for this joke,

01:45:56.420 | which is that there are two kinds of Stanford faculty,

01:45:58.740 | Stanford faculty with companies

01:46:00.220 | and Stanford faculty with successful companies.

01:46:02.740 | So we'll see what comes down the pike from that.

01:46:05.960 | But I mean, many of the technologies and discoveries

01:46:09.100 | that have been made at Stanford have spun off into,

01:46:12.020 | there are these little companies like Genentech

01:46:14.500 | and other companies like that

01:46:16.060 | that are not strictly Stanford relations,

01:46:18.660 | but of course other universities too.

01:46:20.300 | But universities are where the basic research is done,

01:46:22.780 | and then somebody has to implement those.

01:46:24.580 | - Stanford's getting much better.

01:46:25.700 | When I came to Stanford in 1974,

01:46:28.340 | the medical center was more like an NIH of the West,

01:46:34.300 | and there was not a lot of clinical excellence

01:46:37.300 | except for cardiac surgery, Norm Shumway,

01:46:40.700 | and radiation oncology, Henry Kaplan,

01:46:44.380 | who had developed the first radiation method

01:46:47.580 | for treating lymphoma.

01:46:48.700 | And we were great at making basic discoveries,

01:46:53.020 | not very good at translating them,

01:46:55.400 | but over the last, what, 50 years,

01:46:59.340 | Stanford has gotten much better at translating them

01:47:04.540 | into clinical therapies,

01:47:08.060 | and even doing some of that work at Stanford,

01:47:10.340 | not farming it out to other places.

01:47:12.360 | So I think that's another area that we need to encourage.

01:47:16.100 | - Well, the proximity to big tech

01:47:18.340 | is sort of built into the fabric of the Bay Area now.

01:47:24.740 | There's just no escaping that.

01:47:26.300 | And I think overall, it's not without its sometimes issues,

01:47:30.380 | but overall, I think it's a really good thing,

01:47:32.440 | facilitates the most rapid possible flow

01:47:35.460 | between basic science discovery

01:47:37.340 | and implementation at large.

01:47:40.460 | I want to make sure that we cover

01:47:43.140 | just a little bit about vagal stimulation.

01:47:45.460 | A lot of listeners to this podcast

01:47:46.860 | are familiar with the vagus nerve

01:47:48.100 | as this very extensive pathway

01:47:49.460 | connecting brain and body in both directions.

01:47:51.660 | The common idea out there

01:47:55.780 | is that the vagus is associated with calming

01:47:58.780 | because it's in the parasympathetic arm

01:48:00.580 | or the autonomic nervous system,

01:48:01.820 | the so-called rest and digest pathway.

01:48:03.360 | But I happen to know,

01:48:04.660 | and I'm sure you know from experimentation

01:48:06.620 | and from clinical work,

01:48:08.380 | that oftentimes vagal stimulation

01:48:10.020 | is a way of bringing, say, depressed patients

01:48:11.840 | up to more alertness.

01:48:13.180 | That vagal stimulation is not always about calming.

01:48:16.060 | It can be about alerting the brain

01:48:18.700 | or making the brain more alert.

01:48:20.980 | So what sorts of vagal stimulation are you doing?

01:48:24.300 | Given that the vagal pathway is so extensive,

01:48:29.300 | like which branch of the vagus do you stimulate?

01:48:31.580 | There's, it goes around the ear.

01:48:32.900 | It's in the neck.

01:48:33.740 | It goes down through the gut.

01:48:34.580 | I mean, we're talking basically about a superhighway of,

01:48:37.620 | I mean, it kind of reminds me of the Austin freeway system.

01:48:39.820 | If you've ever driven in Austin,

01:48:40.940 | it's like the freeways go in every which direction.

01:48:43.540 | And so whenever I'm there,

01:48:44.380 | I'm like the freeway system here is kind of like the vagus.

01:48:46.140 | So which avenue do you stimulate

01:48:48.980 | in order to get a desired effect?

01:48:50.800 | - Right, well, for stroke,

01:48:52.340 | and as I alluded to,

01:48:54.820 | vagal nerve stimulation coupled with physical therapy,

01:48:58.060 | physical activity, very intensive,

01:49:00.620 | was the very first FDA approved treatment

01:49:04.180 | for chronic stroke patients.

01:49:05.740 | That was approved in 2021, three years ago.

01:49:10.220 | And it was shown in the study

01:49:12.380 | that compared with non-stimulation,

01:49:16.620 | in other words, putting the stimulator on,

01:49:18.340 | but not stimulating and doing the therapy,

01:49:22.060 | that patients did better.

01:49:23.900 | It was a modest improvement, but it felt to be meaningful.

01:49:29.300 | And it was shown to be effective at 90 days,

01:49:32.380 | only three months.

01:49:33.540 | Now, recently at the last international stroke meeting,

01:49:39.540 | this past February, it was presented,

01:49:42.980 | and I don't know if it's been published yet,

01:49:45.020 | that those results hold up for up to a year.

01:49:49.920 | So the way it works, presumably,

01:49:53.580 | is that you stimulate the entire vagus nerve in the neck.

01:49:57.460 | And it's not the peripheral effects on the heart

01:50:00.500 | or the other autonomic organs where it's working,

01:50:04.620 | it's stimulation that goes back to the brain, right?

01:50:09.260 | 'Cause when you stimulate a nerve,

01:50:10.780 | it doesn't go in one direction.

01:50:13.260 | And that's probably how it works for depression also,

01:50:15.660 | not a systemic, but,

01:50:17.340 | and the vagus has lots of connection

01:50:19.700 | with brain functions, right?

01:50:21.500 | And so that's, it's not completely clear

01:50:25.940 | which areas are being stimulated

01:50:28.060 | to recover from stroke or improve depression,

01:50:31.900 | but it's brain stimulation that somehow,

01:50:35.540 | again, resurrects circuits

01:50:37.940 | or induces plasticity in circuits.

01:50:40.460 | Again, it's something that we're learning about.

01:50:46.100 | And I think not just vagal nerve stimulation,

01:50:49.060 | but stimulation of the brain is becoming

01:50:52.660 | a very important innovative treatment

01:50:56.100 | for many brain diseases and injuries.

01:50:59.020 | - Is the vagal stimulation,

01:51:01.180 | is it invasive or can you use an external stimulator?

01:51:04.900 | - It's invasive.

01:51:06.100 | You have to do an operation.

01:51:07.700 | It's low risk, very few side effects.

01:51:11.080 | Occasionally there are some,

01:51:12.700 | it can cause some problems with swallowing,

01:51:15.460 | which are usually temporary, right?

01:51:18.020 | 'Cause the vagal nerve,

01:51:20.300 | the recurrent vagal nerve supplies the larynx,

01:51:23.380 | the vocal cord.

01:51:24.260 | But, so it's an implanted stimulator,

01:51:29.300 | but the stimulation can be turned on and off

01:51:31.740 | with an external magnet device.

01:51:35.640 | - Incredible.

01:51:36.500 | Gary, Dr. Steinberg,

01:51:39.500 | I want to thank you for several things.

01:51:41.960 | First of all, for coming here today to share with us,

01:51:46.040 | right up until the point we hit hot mics,

01:51:48.480 | meaning we started recording,

01:51:50.540 | you were getting calls about patients.

01:51:52.100 | I know you're still in the operating room.

01:51:53.720 | You were our department chair for more than two decades.

01:51:57.140 | - 25.

01:51:57.980 | - 25 years, thank you for that.

01:51:59.700 | And, you know, still just so active in this area

01:52:04.100 | doing cutting edge research and stem cells

01:52:06.420 | and so much more.

01:52:07.860 | So as an extremely busy person

01:52:09.420 | who has many important duties,

01:52:11.140 | you are literally a brain surgeon,

01:52:13.600 | to take the time out of your schedule

01:52:15.180 | to come here and share with us all this information

01:52:17.940 | about how to keep our brain healthy,

01:52:20.060 | the relationship between alcohol and nicotine.

01:52:22.540 | Fortunately, caffeine's not on the list,

01:52:24.140 | but don't overdo it, folks.

01:52:25.820 | Neuroprotection, the discussion about TBI,

01:52:28.540 | something we've never discussed on this podcast,

01:52:31.740 | transient ischemic attacks,

01:52:33.580 | and just a really vast survey of things

01:52:37.340 | that concern a lot of people,

01:52:39.140 | and that also now having heard what you've shared,

01:52:43.040 | also puts them in a position now to empower themselves,

01:52:46.860 | to take some agency over their brain health,

01:52:48.820 | which is something that I think most people really fear,

01:52:51.660 | that this thing inside our skulls

01:52:53.500 | is outside the reach of our efforts

01:52:55.180 | to try and maintain health.

01:52:56.340 | And clearly you've explained how that is not the case,

01:52:59.320 | and there are things we can do to both protect ourselves

01:53:01.500 | and to overcome challenges should they arise.

01:53:03.480 | So on behalf of myself and all the listeners and viewers,

01:53:06.860 | I just want to say thank you so much,

01:53:08.420 | and hopefully as these trials continue to develop,

01:53:12.740 | you'll come back and update us on the progress.

01:53:14.980 | - Andrew, it's been a real pleasure.

01:53:16.380 | Thank you for inviting me.

01:53:17.980 | - Thank you for joining me for today's discussion

01:53:20.020 | with Dr. Gary Steinberg.

01:53:21.580 | To learn more about the research

01:53:22.820 | in the Steinberg Laboratory and Clinic,

01:53:24.780 | please refer to our show note captions.

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01:54:26.420 | in the form of brief PDFs of one to three pages

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01:54:33.620 | deliberate heat exposure.

01:54:34.580 | We have a foundational fitness protocol,

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01:54:51.220 | Thank you once again for joining me

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Dr. Gary Steinberg: How to Improve Brain Health & Offset Neurodegeneration

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