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

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

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Gary Steinberg, Andrew Huberman
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May 20, 2024
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0:00
Welcome to the huberman Lab podcast where we discuss science and science space tools for everyday life.
0:09
I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford School of Medicine. My guest today is Dr. Gary Steinberg, Dr. Gary Steinberg is a medical doctor PhD professor of neurosurgery neurosciences and neurology at Stanford University School of Medicine. He is a world expert in what is called the cerebrovascular architecture of our brain, which is a scientific term explaining how blood flow to the brain supplies oxygen and critical nutrients to our neurons are nerve cells as well as playing a critical role in removing waste products from our brain in order for our brain to function normally during today's discussion. He explains in very clear terms how blood flow to the brain occurs and how disruptions in blood flow in things like stroke and aneurysm impact brain functioning. We also discussed concussions and TBI or traumatic brain injuries, which unfortunately are very common and what can be done to treat concussion and traumatic brain injury, Dr. Steinberg also shares with us recent findings from his laboratory and Clinic revealing how
1:09
How stem cells can be used to recover function in the human brain and spinal cord after things like concussion TBI stroke and other disruptions to the cerebral vascular architecture and he shares with us the science supported tools that is protocols that any of us can use to improve the health and functioning of our brains. So if you or somebody that you know has experienced concussion or traumatic brain injury stroke or aneurysm today's discussion is sure to include Vital Information for you. And for those fortunate enough to not have experienced those conditions today's discussion will also review the latest science and protocols for improving brain health before we begin I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford it is however part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that theme. I'd like to thank the sponsors of today's podcast. Our first sponsor is 8 sleep 8 sleep makes Smart mattress covers with cooling Heating and sleep tracking capacity. Now, I've spoken many times before on the
2:09
This podcast about the fact that sleep is the critical foundation for mental health physical health and performance Now 1 of the key things to getting the best possible night sleep is to control the temperature of your sleeping environment. And that's because in order to fall and stay deeply asleep. Your body temperature actually needs to drop by about 1 to 3 degrees. And in order to wake up feeling refreshed and alert. Your body temperature actually has to increase by about 1 to 3 degrees 8, Sleep mattress covers make it extremely easy to control the temperature of your sleeping environment and thereby to control your core body temperature so that you fall and stay deeply asleep and wake up feeling your absolute best. I've been sleeping on an 8 Sleep mattress cover for about 3 years now and it has completely transformed the quality of my sleep for the better 8 sleep recently launched their newest generation of pod cover the Pod for Ultra the Pod 4 cover has improved cooling and heating capacity higher Fidelity sleep tracking technology and the Pod 4 cover has snoring detection that will automatically lift your head a few degrees to improve air flow and stop your snoring. This is really important snoring is associated with some
3:09
Something called sleep apnea and sleep apnea is known to disrupt brain health and body Health in a number of ways put differently being able to breathe clearly throughout the night is essential for not only feeling rested when you wake up but also for brain health and body Health if you'd like to try an 8 Sleep mattress cover, you can go to 8 sleep.com huberman to save $50 off their pod for Ultra 8 sleep currently ships to the USA Canada UK select countries in the EU and Australia again, that's 8 sleep.com huberman. Today's episode is also brought To Us by Roka Roka makes eyeglasses and sunglasses that are the absolute highest quality. Now, I've spent a lifetime working on the biology of the visual system and I can tell you that your visual system has to contend with an enormous number of different challenges in order for you to be able to see clearly Roka understands this and has developed their eyeglasses and sunglasses. So that regardless of the conditions you're in you always see with the utmost Clarity Roka eyeglasses and sunglasses were initially designed for use in sport in particular.
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Things like running and cycling now as a consequence. Roka frames are extremely lightweight so much so that most of the time you don't even remember that they're on your face. They're also designed so that they don't slip off if you get sweaty now, even though they were initially designed for performance in sport. They now have many different frames and styles all of which can be used in sport but also went out to dinner at work essentially any time and in any setting if you'd like to try Roku glasses, you can go to Roka. That's r o ka.com and enter the code hubman to get 20% off again. That's roka.com and enter the code hubman to get 20% off. Today's episode is also brought To Us by Aeropress Aeropress is like a French press but a French press that always bruise the perfect cup of coffee meaning no bitterness and excellent taste Aeropress achieves this because it uses a very short contact time between the hot water and the coffee and that short contact time also means that you can brew an excellent cup of coffee very quickly. The whole thing takes only about 3 minutes. I started using an Aeropress over 10 years ago and I
5:09
Learned about it from a guy named Allan Adler who's a former Stanford engineer who's also an inventor. He developed things like the Aerobie frisbee in any event. I'm a big fan of Adler inventions. And when I heard he developed a coffee maker the Aero, press I tried it and I found that indeed it makes the best possible tasting cup of coffee. It's also extremely small and portable. So I started using it in the laboratory when I travel on the road and also at home and I'm not alone in my love of the Aeropress coffee maker with over 55,000 5-star reviews Aeropress is the best reviewed coffee press in the world. If you'd like to try Aeropress, you can go to aeropress.com huberman to get 20% off error, press currently ships in the USA Canada and to over 60 other countries around the world. Again, that's aeropress.com huberman, I usually mention this at the end of episodes, but if you're learning from Andor enjoying the huberman Lab podcast, please click the Subscribe button on YouTube and if you listen to the podcast on Spotify or apple, make sure you click the follow tab on Spotify and or apple and on both Spotify.
6:09
To find Apple. You can also leave us up to a 5-star review and now for my discussion with Dr. Gary Steinberg.
6:16
Dr. Gary Steinberg welcome
6:18
Thank you, Andrew pleasure to be here.
6:21
I have a lot of questions. I know people are interested in keeping their brains healthy and sadly things happen to the brain. Um, sometimes as a consequence of Aging sometimes as a consequence of certain activities, maybe you could just explain for us right off the bat.
6:37
What is a stroke? What is an aneurysm? What is a hemorrhage where do these terms overlap? How are they different? Obviously, none of us want these things. Um, and we will talk about ways to prevent them and your ways of treating them as well, of course, but just to start off maybe we can just lay down the nomenclature.
6:56
Sure. So a
6:56
stroke is like a heart attack of the brain.
7:00
Uh, it involves disruption of blood flow to the brain either in the form of a blocked vessel.
7:06
Or less likely a hemorrhage about 87% of Strokes are due to uh a clot either forming in the brain artery itself or forming, uh closer to the heart in the heart or in the corded artery and dislodging and blocking blood flow to the brain about 13% are caused by a hemorrhage bursting of a blood vessel.
7:31
And that results in lack of oxygen and glucose being delivered to the brain cells and that ultimately causes death of tissue and disruption of bodily functions neurologic function. That's what a stroke is.
7:46
How do we know if we have a clots residing in our body that could be dislodged? Um, I know that some people when they fly where where compression socks. Um, I know that some people have genetic mutations that affect clotting. I'll raise my hand here and uh, I'll do a disclosure. I did some genetic testing. I am a heterosexual for um Factor 5 Liden which is a clotting Factor. Um, heterosexual folks means I have 1 mutant copy, so fortunately I don't suffer from excessive bleeding or clotting but there are lifestyle factors that can exacerbate a an existing, um mutation like that. People are homozygous mutants for Factor 5 Liden, of course at much greater risk for um, clotting and bleeding. Um, so I just disclosed a lot. Um, maybe you could comment on some of the clotting factors and lifestyle factors that impact clotting but how would somebody know if they're like, they've got a clot that could potentially go to their
8:46
Brain, sure. Well, you might not know in many cases. You don't know. Uh, and that's the problem. You can have uh a predisposition as you say due to uh, certain genes that are mutated or uh represented that predisposed to to clots and those clots can occur on the arterial side or the venous side.
9:10
The arterial side is what generally causes a stroke an esmic stroke, uh on the venous side. You can sometimes uh have problems. Uh, when you talk about flying, um, not moving your legs developing clots in your legs wearing compression boots that's on the venous side and that can cause uh, something like a deep vein thrombosis, uh, which is not good because it can travel to the lung and cause a pulmonary embolus that generally on the venous side does not go to the brain. Oh good in my case that feels unfortunate. Yeah, exactly. Uh, you can develop some venous problems in the brain, which can cause a Venus trip type stroke. That's much less common. And the way that causes the stroke is not lack of blood flow being delivered to the brain, but
10:01
By having a clot in an important vein the blood can't get out of the brain. It backs up and causes swelling or edema. Uh, but that's much less common. Uh, generally we talk about Strokes as being uh arterial in nature. Um, and you know, either that either blockage of a blood vessel or bursting a of a vessel.
10:25
What are some things that impact clotting and or excessive bleeding? Um, my understanding is these Factor 5 light and mutations are 1 example. The other is um, let's say somebody takes say a a blood thinning, um agent like baby aspirin or um, I told and I I'll have to check this. I'm sure people will say in the YouTube comments that if you take lots and lots of say fish oil or things like that. You can become more of a bleeder some are uh people out there are hemophiliacs and then my understanding is also that certain forms of oral contraception for women can increase uh the rates of bleeding. Um, so tell me if I'm wrong about any of those and if any of those things predispose people to more stroke or hemorrhage,
11:11
Sure. So, um different kinds of drugs, um thin the blood and they um can predispose you to having a larger Hemorrhage, uh than you would if something uh bursts or if you uh fall and have some traumatic injury to your brain or anywhere in the body.
11:33
Uh in general they don't cause a hemorrhage because they're fairly safe. But uh if there's as I say some, uh, it's it's some Interruption, um to the to the body, um, like a bruise. Um, it would be a much worse. Um type of bleed
11:51
Uh, so aspirin is a type of antiplatelet agent that thin some blood there are many types of antiplatelet agents and they're very very, uh useful for treating people who have uh, a a predisposition to develop clots because they thin the blood anti-coagulants are another type. Uh, they're they're they're called. Uh, they're known as Coumadin borin eloquest. There's lots of lots of new agents. Um, and uh, they're often taken orally or can be given intravenously. Uh, Heparin is another 1, uh, again, they thin the blood so they would uh, put someone at somewhat increased risk for hemorrhage.
12:32
Um, then uh, as far as oral contraceptives, if you go back to the 1970s when the uh, oral contraceptives were first generation were coming out.
12:44
Uh it turns and they were heavily estrogen, um dominated rather than progesterone. Um, they did and they still to some extent increase the risk of developing clogs. So women back in the 70s who took oral contraceptives and smoked
13:03
had a very very high incidence of developing, uh, clots and and schemes and clots elsewhere in the body.
13:12
The newer Generations, uh are are much safer in terms of De developing clots, but for my patients, uh, many of whom have had Strokes or at risk for stroke. We recommend that the women do not take oral, uh contraceptives that they use some other form, uh, IUD for instance may have a little bit of uh progesterone which is released locally, but it doesn't cause a large increase in estrogen or or progesterone systemically.
13:42
So we still believe that the oral contraceptives, uh, increase the risk somewhat not the way it did for first generation. And then there are other modifiable factors besides the genetic ones.
13:54
So smoking is a very uh, high risk factor for developing, uh clots, um, which can lead to Strokes heart attacks peripheral vascular disease.
14:07
Um High lipids is another.
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so when people have high
14:15
bad cholesterol LDL, it's recommended, uh that if they can't reduce it with diet that they take a Statin. Um, the statins are very very effective in lowering the bad cholesterol preventing strokes and heart attack interestingly. The statins have also been shown to be highly beneficial for the for the blood vessel Integrity even if you don't have high LDL interesting so they have other beneficial properties. So again for my patients, I often recommend they take a Statin even if they don't have high cholesterol.
14:50
Interesting and then hypertension is another uh, risk factor for for developing, uh,
14:56
clots and and arterial disease when you say that smoking dramatically increases the risk of stroke is that because of nicotine per se is it the uh Vaso constriction and blood pressure elevation that comes from nicotine itself or is there something about smoking maybe even vaping? I don't know that um, the contaminants the other chemicals, um in cigarettes or vape chemicals that increase the stroke risk, or is it nicotine itself? It's not just nicotine nicotine
15:25
is 1 of the factors, but it's the other uh products that are produced by by smoking that
15:32
that can have an effect. So given that so many fewer at least Americans and I think worldwide, um, people are smoking less. Uh, are we seeing less stroke?
15:42
Yes, the the incidence of stroke is
15:44
actually decreasing. Um, it may be in part due to decreased smoking but it also is in part due to uh, other modifiable factors. So hypertension is much better, uh treated now than it used to be people take better care of themselves in terms of other lifestyle factors. So people uh exercise more there's a lower incidence in some subgroups of uh, obesity. Those are the risk factors also for for developing strokes and as well as heart attack,
16:19
What is the relationship between heart health and brain health as it relates to stroke? Uh, I would imagine that anything that's good for our heart is probably good for our brain, um given the enormous amounts of blood and glucose that the uh, the brain requires to function
16:36
normally. Yeah. It's it's a good point in general. Uh, the things that are good for the heart are good for the brain there. There are differences between the heart and the Brain but uh, they they both, uh, depend very much on blood flow the brain's unique though, because the brain
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represents only 2% of the body weight
16:58
yet it draws 15% of the total blood flow.
17:04
And remarkably it consumes 20% of the body's oxygen.
17:10
So the brain I still think the brain is the most important organ, uh, not the heart not the kidneys, but I'm biased of course. Yeah, you've spent some time in
17:19
in uh in the landscape of the brain. Yeah. It's it's clear that um,
17:24
Of all the tissues in the body if you had to pick 1 tissue to remove 1, you know cubic millimeter of that tissue that your brain and probably the neural retina would be your least, uh favorite. Um,
17:37
Choice just given the deficits that can result right? And of course the brain also has what makes us human right speaking of which if we take a little departure into a neurosurgery itself your your specialty. Um,
17:51
Of all the years of of doing brain surgery. Um
17:56
Can you recall maybe 1 of the most incredible moments or days, um that allowed for some insight into how the brain works by virtue of let's say stimulating and given brain area or removing a given brain area or or something of that sort. I asked this because um, you know, so very few of us will ever have the opportunity to do what you do and if I were here talking to an astronaut and by the way, I can sort of neurosurgeons the astronauts of Neuroscience. Um, if I were sitting here with an astronaut I'd say, you know, tell me something interesting about being in space that I wouldn't know from looking at pictures or videos of it. What is an example of maybe 1 of the more, um, profound, um, Insight stimulating moments, um
18:38
from doing brain surgery there. I mean every every patient is different so I'm always learning and that that's why uh, I still enjoy it that it's a challenge. Uh, and you have to think quickly. Um, it's not a it's not simply mechanical but for instance a couple weeks,
18:56
Ago, uh, I had a patient who had a vascular mouth formation, which was located. Uh, we thought right in her speech area.
19:06
So in order to operate safely, uh first we did a what's called a functional Mr. Scan before surgery and that gives us some idea.
19:15
Of where the speech area is we can map it out on an MR scan.
19:20
And the way it's mapped out is um, we have the patient, uh awake, uh talk to us when they do the scan and because there's a coupling between blood flow and and the neuronal activity.
19:36
Uh, when the speech area and the language area is stimulated by talking.
19:42
Uh, there's increased blood flow to that area and we can see that on an MR scan. That's how the Mr. Scan works.
19:48
So we have some idea that this was very close. If not in the speech area, but the most accurate way of determining that is to operate on the patient.
19:59
with her awake
20:01
So we took what we did was we sedate the patient. We don't put a tube down and induce general anesthesia.
20:08
We numb up the scalp.
20:10
We take off a piece of bone after cutting the scalp.
20:13
Open the membrane covering the brain called the dura and then we allow the patient to wake up more from the sedation.
20:22
And then what I did on this particular patient was to use a uh, tiny stimulator.
20:29
A little probe and I can stimulate areas of her cortex with her awake.
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And see if the stimulation impairs her ability to speak or understand language.
20:42
and quite surprisingly their uh was no activity in the corridor that I chose sometimes when we see, uh an area that
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Is involved with speech that's eloquent. We have to choose a different Pathway to get to the underlying vascular problem. And so that's what we did in this case.
21:04
And um, she talked to us the entire case she told us about her daughter, uh who uh was uh, very involved in um debate and all of her successes while we were operating while I was taking out this vascular malformation, uh, under 20 magnification with very special instruments. I use a laser now, which has a diameter of the fiber optic cable. Uh, the laser, uh tip is 0.5 millimeters so that I think is the gentlest way
21:37
Other times I've been surprised um, uh about brain function is uh, operating deep in the brain is a part of the brain called the brain stem which you know, well, it's a small area that connects the phalam. Those are the signals coming from the cortex go through the thalamus to get down to the face arm and leg to move the muscles and all the sensory information which comes from the arms and legs and face goes through the brain stem up to the thalamus and then to the cortex.
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In this area, although it's very small.
22:13
Are contained uh, very closely packed fiber tracks and nuclei. Those are the cell bodies are very important neurons.
22:22
And when I trained back in the 80s, we never operated in that area because we couldn't do it safely.
22:30
with developments in computer technology and imaging and anesthesia we can now
22:38
Find safe corridors to get into the brain stem and sometimes we stimulate for other Pathways not language, but other Pathways and I'm continually amazed um this last week I took out um 2 vasel malformations.
22:54
Um, and they're not big. I mean, they measure between 8 millimeters and a centimeter but they can wreak havoc in the brain send because it's such high price real estate and these had bled but I found a safe card to go through I took it out and I'm amazed that you hardly set the patients back in some cases because in the past we would have clobbered the patients doing
23:18
that amazing. Yeah. It's a remarkable to me how much can be done now with imaging so visualizing the brain and being able to Target a specific location and you mentioned Fiber Optic Cables also heard of things like the gamma knife and lasers. So how much of neurosurgery nowadays is actually burrowing down through the brain to a given location to stimulate or remove tissue versus um, you know, using these laser or Fiber Optic approaches to sort of triangulate and get to something without having to basically drill down through the brain right
23:49
neurosurgery is becoming much less invasive and this is something
23:54
something that I really try to push when I was a chair of the department for 25 years at Stanford. Um, so minimally invasive techniques include
24:05
operating through the vessels.
24:08
Right. So now my I don't do this myself, but my colleagues some of whom are neurosurgeons some are Interventional Radiologists. They can go through the groin in the femoral artery or through the radial artery.
24:19
They can thread a catheter backwards.
24:23
Into the brain from the groin they can go up.
24:27
Into the aorta then up into the corded artery.
24:30
From there. They can go up into the brain arteries the middle cerebral artery and they can treat some of the uh, hemorrhagic problems like aneurysms by deploying from genetic coils there or new devices.
24:45
They can pull clots out if there's an acute stroke from a clot in an artery in the brain. Wow, it it's really it's really quite impressive.
24:54
Um, then we've we and others have developed techniques to use Focus radiation, um on the brain and that's called radio surgery. So examples of that are gamma knife. Um cyber knife was invented at Stanford by 1 of my colleagues actually and this uses, uh beams of radiation. Gamma knife uses a Kobalt Source multiple, uh sources of cobalt.
25:22
The cyber knife uses x-rays, uh, when I started I was very involved with using cyclotron generated heavy particles, like helium and proton and they can be focused.
25:36
And the advantage of this is you don't have to open the skull.
25:40
You focus it on a very small area.
25:43
And you can eliminate um vascular malformations called arterial venous malformations tumors.
25:50
You can even use it for some pain conditions like trigeminal neuralgia. It's not risk-free because even though radiation is not is doesn't require opening the skull. It still is a form of energy. That's damaging that that's how it works. It causes for the avms. It gradually clouds off the blood vessels, but it's much easier and much safer than some of the invasive techniques that we use we operate now through tiny openings, even when we do open surgery.
26:20
When I trained we used to shave the whole head.
26:23
We would open a huge area of the of the skull now. We operate through tiny are very small areas. When I take out vascular malformations, uh in the brain stem for instance. Uh, I sometimes operate through openings in the side of the brain stem that are 2 to 3 millimeters.
26:42
Wow.
26:43
Um, another form of non-invasive, uh treatment that neurosurgeons use is called focused ultrasound again, it's you don't have to open the skull it focuses, uh sound waves.
26:57
Um on areas of the brain we're using that to treat uh, essential tremor or um, uh Parkinson's disease. Um, it's starting to be used for treating tumors.
27:12
So these are all advances that um, we're not present when not when I trained another way of treating, uh, minimally invasive although it still requires a hole in the head is to put in an electrode.
27:25
and stimulate the brain so that uh was first used for treating Parkinson's disease very effective for medically intractable Parkinson's
27:35
It's used to treat chronic pain.
27:38
Recently, it was shown to be beneficial, uh for epilepsy. In fact, there are 2 major trials prospective randomized trials that were done, uh were led by uh, Physicians, uh, neurologists at Stanford and showed the benefit of um, stimulation of the brain to to treat uh, very difficult. Um epilepsy.
28:00
So this I think is going to be the future is minimum more and more minimally invasive. In fact, we're using some of these techniques to even treat um psychiatric disorders, like depression of tests of
28:11
compulsive Behavior incredible. I should have asked this earlier but um Tia's transient es scheme attacks. Um, I think most people assume or know that the symptoms of stroke include, you know, sudden weakness, maybe Hemi paralysis of the face confusion slurring of the words, of course, these symptoms can be the consequence of other things as well. Um, what are some of the symptoms of transient esem attacks? And is there anything that people can take for transient schema attacks and I of course would love for you to inform us, uh, what a transient esem attack is,
28:46
right. So a transient schematic attack or Tia is a reversible stroke.
28:53
Uh, it results in a temporary loss of function such as uh, inability to move partial paralysis or complete paralysis, but then it resolves.
29:05
uh inability to speak visual problems double vision blurred vision loss of vision, uh, it can cause uh slurred speech
29:15
Uh or difficulty understanding language imbalance problems walking even cognitive problems. So it can vary depending on what part of the brain it affects.
29:25
in the past it was defined as a neurologic deficit due to lack of blood flow that lasted less than 24 hours, but
29:35
Now that we have such sophisticated Imaging like Mr. Scan some of these patients who have a TI what would have been considered a TIA before lasting minutes or up to 24 hours on Mr. Scan have been shown to have a little stroke.
29:51
So now the definition is a little different if there's an if you do an MR scan and it shows a new abnormality a new stroke, then it's called a stroke rather than a TIA. Um, so there's a little overlap there but it's a temporary, um loss of of neurologic function due to lack of lack of blood flow or in some cases a hemorrhage.
30:14
My understanding is that people can also have strokes in their spinal cord. Um, because spinal cord tissue is after all central nervous system tissue, I think most people don't realize this but the the tail end of the brain the the brain stem as we're talking about before essentially extends down the uh, the spinal column, uh, sort of like a a long tail, right? Um, uh, uh down to uh, the base of the pelvis really, um, so we call it the spinal cord, but it's all brain. It's contiguous with the brain. So, uh, how often do you You observe um, spinal strokes and what are some of the
30:51
Symptoms of spinal stroke.
30:52
Yeah, it's much less common, um than uh, a stroke involving the brain, uh, probably because there's less tissue involved. Uh, the spinal cord is supplied by um, an anterior spinal artery. That's an artery on on on this side
31:09
and by 2. So for those listening sorry, it would be the um on the stomach side of that of the body. Yeah, exactly.
31:16
And it's supplied by 2 arteries posterior spinal on the back side.
31:23
So if there's an interruption to blood flow in any of those arteries, it can cause death of tissue in the spinal cord. And that would result in a neurologic deficit depending on where it is.
31:37
So if it occurred on the stomach side that whole artery which supplies the the 2/3 of the spinal cord, um on the stomach side, uh, and it involved both sides of the spinal cord, it would cause uh paralysis of both legs.
31:57
And a partial sensory, uh deficit would cause loss of pain and temperature because that's where those pathways are.
32:04
If the problem was on the back side of the cord, it would cause a problem potentially with uh, a light touch sensation in the legs. Um, if it was below the um, it was in the below the cervical region, uh, and uh problems with what's called proprioception. That's the ability to recognize where uh, your position of your joints is so it depends on where it is. Um, some of the uh, uh vascular problems I deal with actually do involve the spinal cord.
32:36
And you can develop other problems there. Um, for instance you can have a direct connection between a abnormal artery and a vein in the spinal cord, which doesn't cause a typical Stroke by blocking blood flow, but it causes more of that venous problem we discussed where there's so much blood going directly from the artery to the vein bypassing the capillaries that the veins become engorged the blood can't get out of the spinal cord and the spinal cord becomes congested and patients can present with problems, uh, walking or uh sensory problems.
33:15
If the uh spinal cord is involved in the cervical region up high, then the arms can be involved as well.
33:22
I see I should have asked this earlier. But is there any relationship between alcohol intake and the propensity for stroke or Hemorrhage or any of these other things?
33:30
Yeah, that's a good question. Yes, there is uh their their the uh,
33:36
People who who indulge or overindulge uh, uh or at risk for developing, um, uh stroke problems. So it's another contributor contributory Factor.
33:48
Which can promote um problems with the with the blood vessels, um clots, but also Hemorrhage so it can make the blood vessels more fragile. Another factor. I see commonly, um in patients who develop aneurysms, those are blisters on the blood vessels in the brain and they're like little balloons and as they enlarge they rupture just like a balloon can burst
34:12
um
34:13
some of the patients I see uh are not just smokers but indulge in other drugs, so cocaine metamfetamin increase the risk of developing these aneurysms or developing Hemorrhage bursting of a blood vessel.
34:29
And is that because those drugs tend to increase blood pressure during their use, um, it's because they
34:36
damage the vessels.
34:38
And they also can cause hypertension. Yes, it's both factors. So when I operate on uh on these patients and looking at the vessels, um, they are rad they're ragged. They're very thin. They're not normal vessels. They lack structural Integrity. So it contributes to the development of of poor vessel integrity and drugs like cocaine and amphetamine can jack the blood pressure up, uh, and that could cause a hemorrhage in these these um,
35:08
problematic vessels. Yes, so it sounds like the message is clear, uh avoid cocaine use avoid methamphetamine use and avoid excessive alcohol intake if you want to avoid stroke
35:20
right and throw smoking in there too. It's interesting because for a lot of years there was so much discussion about
35:26
red wine being good for heart health. Now, it's debated the moment. I say that people will send a bunch of studies that say, yes, I my stance on the more recent data is that if you had to pick you drink less or not drink,
35:38
Drink as opposed to drink. Um, but I'm curious what your take is.
35:41
Well, you know, this is interesting and um, I'm always quite amazed at at um, the way people change their behavior based on 1 study that comes out even if it's a good study. So yes, it used to be um, uh considered beneficial if you drank red wine and then for a while it uh studies showed any wine was beneficial in moderation.
36:06
And um and that used to be 2 drinks a day for men 1 drink a day for women and then the latest studies which have been surfacing this year suggests. No alcohol is good. Yeah, but you know next year may be that we're back to oh, you know wine is the best thing you can do for your in moderation for your your brain and heart health. So it yeah It's Tricky my read of the data
36:30
and here I mean the data across multiple certainly not every study but multiple studies is that um zero to 2 drinks per week. It's seems to be the range that everyone agrees is safe at least for non-alcoholic adults. Um, and then once you get out past 2 drinks per week is when gets into the gray Zone where some people say, it's good some people say it's neutral some people say it's bad, but that once you get up past, you know, 4 or 5 servings of alcohol per week. It's pretty clear to me. It's not a good situation. Well,
37:00
that was the prevailing Theory until this year and I don't know if you've kept up but in the
37:06
past, you know few months there have been several articles published saying, um
37:12
No W. No alcohol is good. But then you have to balance that against the fact that alcohol um for many people tends to relieve stress. So, um, you know, if you're relieving stress, maybe a counteracts any adverse effects so complicated issue. But yeah, my theory is um moderation is the key to life, uh, and you know and uh happiness also we know promotes longevity.
37:41
Absolutely, I I agree with you. I'm not heavy-handed about the alcohol thing. I was just say you know do is do as you wish but know what you're doing. Um, and I think many people who hurt our podcast episode about alcohol who stopped drinking alcohol or who elected to drink less did so I'm told um, because they really didn't enjoy it that much to begin with so it more or less gave them permission to drink less. Um, not that they needed it but they took it. Uh, anyway, I think it's a really interesting area as you mentioned probably lowers, um stress at um, probably also disrupts patterns of sleep and the gut microbiome. So there's you know, you you can't escape in biology. There's always some uh modulatory influence on something else
38:23
exactly.
38:24
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39:56
Speaking of Lifestyle factors, um anytime we hear about traumatic brain injury or concussion people immediately seem to think about football. Um, but I'm told by colleagues of ours in neurosurgery at Stanford and in neuro engineering that most head injuries are not from football. They're not even from sport. They're from construction work accidents. They're from car accidents.
40:19
What is your um take on? You know, somebody let's say um, God forbid gets rear-ended in a in a car accident. Maybe gets Whiplash. Maybe they're feeling a little off. Like maybe they have a minor concussion. Maybe there was some um movement of the brain. That wasn't good.
40:33
What's the going consensus on how to deal with that? Um sleep more but then they tell you not to sleep excessively. Um should people take blood thinning agents. I mean obviously avoid alcohol or certainly don't get another head injury anytime soon. But you know, what do we know about TBI and concussion that that can help people move through that period in the in the weeks and months afterwards where it's really scary, you know, if you've ever had a hard head hit, you know, and they go they might scan you. They might not see a bleed but it's it's kind of scary when you feel a little bit off because you've been hit in the head.
41:06
Yeah. It's a great question and there's a lot of interesting concussion now, um, I got very involved in this back in the 90s because I was the 49ers neurosurgeon, um for a decade from 1990 to to 2000. How are they doing in that point? I remember the dynasty of the 80s
41:24
or the 90s are
41:25
good. Oh, they they were in Super Bowl contention. In fact, uh, I took care of Steve Young.
41:30
Yeah. He's a local guy
41:32
who ya Steve's a great guy and
41:33
A really smart guy. Um, uh, he in fact, he has a a a degree from uh, Brigham, uh, young, uh, Steve was quarterback then and they were in Super Bowl contention and uh, Steve had had some uh concussions and um, I actually sent him back to play when he recovered so you can examine someone um, uh and get a decent idea of how they were recovering from a concussion. Uh, Steve unfortunately had uh, uh, ah a bad concussion at 1 point and um, he ended up retiring which was the smartest thing. I think uh for him in the end and he's become very involved with um, studying concussions and and uh trying to figure out better ways to um to diagnose them, uh prevent the squella for football players, including uh changes in equipment and and and in in uh tackling and that kind of thing, um, but concussion,
42:34
Is we've learned a lot since the 1990s at that time. Uh
42:39
Concussion, um was not known even repeated concussion to cause CTE chronic traumatic and sealup in football players CTE, which became a hot topic was known only in boxers. So I became very well informed at the time about uh concussions and there was surprisingly little known um, soccer players had a high incidence of concussion, uh at that time, it wasn't known if there were long-term squella and usually there are not long-term squella. Um, as long as you don't get repeated concussions, um,
43:17
so, um
43:19
now what we generally recommend, uh, if someone has a concussion, um, we usually get an MR scan if it's severe Mr. Scans usually don't show anything.
43:31
They would show a contusion if there's any bruising of the brain, but um, they don't show the the the molecular, um abnormalities that occur with a concussion.
43:42
So the best way to um figure out how severe it is and when a when a person has recovered is to do more sophisticated neurologic testing. Uh eye tracking is a very sensitive way, um to to to to detect problems with um with the brain after a concussion because you won't track as well. And in fact many sports, uh football hockey, uh are incorporating, um preseason eye tracking testing. I see to get a baseline to get a baseline. Of course, some of the players will um game the system because they still don't want to be taken out so they may try to perform
44:25
Not as well as they they could on their I track. Uh, yeah on their I see they throw the test. They throw the test. So their Baseline is I mean, you know, I don't think that's very common, but that's the way you can game the system but uh, as long as it's performing, well, that's a very good way, uh of of detecting um subtle problems with the brain and what you're a vision scientist. So you you understand how important um, uh, all the circuits are, um, in terms of and the visual system is unique because it tests, uh the brain from the retina,
45:01
All the way back to the occipital lobe. So it's the whole longitudinal axis of the brain that's being
45:06
tested.
45:07
Yeah, I'm always struck by when I see these News News Real highlights of a you know, a player goes down.
45:14
They stay down. Um, and then, you know, they're helped up and everyone cheers and then they might hobble off take a few moments and then you know, how are they gauging the decision to put the person back in and the reason
45:26
it's perplexing to me how they would determine that is that you and I both know that the neurons the nerve cells in the brain.
45:33
Very likely, um could be injured maybe even on their way to death after a head injury, but that the actual dying off of the tissue could take several minutes hours maybe even days. So putting someone back in to get hit more, um, seems really risky, but at the same time that's their profession that's their choice. And so you don't necessarily want to make the decision to take someone out of a game or a job. Um, or have them stop driving if they don't actually need to stop so it's it's a tricky thing
46:04
it is tricky and I think we have better, uh methods of uh, even at the if you're talking about sports on the sidelines of doing testing. Um, there are neurosurgeons there now, uh who are part of the process. Um, uh,
46:20
As far as recovering, uh in general, it's good to not stress the brain but uh total absence of sensory, you know, uh information sensory deprivation for long
46:32
periods is not a good idea right just staying home in the dark with sunglasses on also not a good idea.
46:37
Exactly. So you want to make sure the brain still has input, but you don't want to um overstress it when you're recovering from a concussion.
46:45
Sounds like doing all the things to keep blood pressure relatively low.
46:49
Um LDL cholesterol relatively low, so interesting what you said earlier that statins might be vascular protective even in the absence of high cholesterol.
46:58
Yeah. There's a lot of good evidence for that. In fact, some Studies have suggested that taking statins reduces the risk of cognitive decline and including conditions like Alzheimer's interesting. I know that statins are a bit of a controversial
47:11
topic, um among listeners because some people um report. I think I have this right that statins can give them a kind of a brain fog if they take the wrong 1 or excessive amounts.
47:21
Uh, yeah, it it I'm not challenging what you're saying. I know no no, it's
47:25
I just hear the shout version in the in the comment section and I'm just I don't take a Statin but my cholesterol is in check. Um, but I hearing more and more about some of these benefits of statins. It's
47:35
interesting. Yeah. Yeah, and the the information is still emerging for a traumatic brain injury in general. You not a good idea to take uh, an aspirin as opposed to a stroke or a TIA where you
47:49
would want.
47:49
Want to take
47:50
it right? Because if you have injuries say you have a contusion to the brain and there's some uh, some traumatic damage taking a blood thinner might cause that to worsen or cause a hemorrhage.
48:02
What about caffeine? Is there any evidence that caffeine can increase stroke risk? Give me I like coffee and I like uh yerba mate tea, so I'd be reluctant to give it up. But I consume it in moderation. Is there any direct relationship there? I don't know any
48:14
relationship. Oh good, unless it unless you're taking so much that your blood pressure is Sky High my blood pressure tends to be lots of benefits, uh, um, evidently to to caffeine in terms of of Health
48:27
I agree with you there. Um, I have a question about something that many people.
48:33
Are starting to do now which is to get um exploratory MRI. I actually did 1 of these. Um, I wasn't gifted 1 I just decided to bite the bullet and pay for it is a whole body scan that put me in the tube did an MRI get everything from tip to toe. Um, and I learned a few things. I learned that I have like a slight. I think it's L3 or L4 disc bulge that explained a little bit of like pseudo sciatica, and I've been able to work around that um and keep that strong. I learned that fortunately for me. I only have 1 white spot on the brain. I was told that you could have 1 per decade. I'm nearing 50. So I feel very lucky there especially given that I've hit my head a few times skateboarding and doing martial arts and things like that. But um, so I feel lucky but I also know people that go in for these scans.
49:19
And get the report that you know, they have a um a growth of some sort or they have multiple white spots as they're called on the brain which is kind of damage to to tissue the neural tissue.
49:30
You know, what is your thought on these? Um exploratory preventive scans. Do you think they're useful? Um, do you feel like they cause undue concern. I mean, this is a new thing people going out and getting their brain scanned. Yeah,
49:43
and people are getting total body scans. So I think there are benefits and risks involved. So the benefits is that you might pick up, uh, something that should be treated like an early cancer, uh, or a large aneurysm in the brain which would have a higher chance to bleed but many times and I see patients all the time who were referred for a tiny aneurysm
50:08
Um blister on a blood vessel in the brain that was found incidentally on a total body scan and these aneurysms which can be 1 or 2 millimeters. Sometimes we don't even consider those as real aneurysms. Um, they don't need to be treated in most cases.
50:27
Um, and so it's uh, it's a little controversial because people can be worried about them. Even if they're reassured other examples. Are you find something in the brain or elsewhere in the body? Not sure what it is and then in order to determine what it is patients start having more invasive biopsies and tests which can lead to what we call attro injuries. That's iatrogenic is caused by the Physicians. So, uh, I think you have to be very thoughtful when you interpret the results of of these um, total body or or or even brain scans and um, I would recommend talking with a specialist about it.
51:10
um, if if if you're concerned
51:12
but um, you know people wonder I have this, uh, we were discussing it earlier today actually, um with 1 of your colleagues and what if you're found to have a 1.75 millimeter aneurysm if it's really even an aneurysm
51:29
Should you change your lifestyle and for something like that? I would recommend know you should forget about it.
51:36
Get a follow-up scan, but you may very well live and die with with this little blister that is of no consequence. So, uh, as I say, I I think you have to be careful about how you interpret and and how you uh act on on these. Uh,
51:52
Findings, maybe we can talk about lifestyle factors because I think anyone listening to this is going to think I don't want to stroke. I don't want transient schematic attack. I don't want Hemorrhage. I don't want any of this stuff and we already discussed a little bit about how what's good for your heart generally is good for the brain. But you know, I think most people strive to eat. Well meaning not excessively also not undereat, um to hopefully eat a lot of unprocessed or minimally processed foods,
52:19
And to avoid smoking perhaps, um avoid alcohol in excess avoid hard drugs, um get exercise. Um, and so, you know, I think people generally try and do all these things get good sleep Etc. Um, but at some level I think everyone also wants to know like when are they in their safest? Um kind of shape for avoiding a stroke is is there sort of a blood pressure cut off where we could say? Okay, you know, if you keep your blood pressure resting blood pressure below blank you're doing pretty well. Um, and if your cholesterol is below blank you're doing pretty well and then you just, you know, while keeping moderation in mind try and live a life that um, you know reduces the probability of getting a stroke or a or some other, you know blood related neural attack.
53:11
Well, I think it has to be individualized to
53:13
some extent and um over time the standards and the guidelines have changed. It used to be if you're systolic blood pressure. That's the upper number was under 1:30, 1:30 or under that was considered normal and and would not lead to problems now.
53:32
The guidelines suggests that 120 or lower is better in large, you know studies.
53:39
But um as an example, uh when my blood pressure gets under 120.
53:45
I feel lightheaded. In fact, I had an event, uh about 15 years ago when I was overdoing it like I shouldn't have been overdoing exercise or overdoing everything. I was in my I was fifth Stanford faculty member that over does something that was a joke
54:01
that among Stanford
54:02
faculty. I was 56 and I operated all day in 2 operation. Um, I got done early. Um, it was in the spring and I took a run up to the dish and then I took a red eye to Houston for a meeting.
54:18
And I emailed on the flight got an hour or 2 asleep went to the meeting was fine. Uh, it was a stroke meeting with a bunch of scientists, uh, neurologists and scientists were about 120 people. There were 2 neurosurgeons there plus me and um drank some coffee at noon. I went for a run because I like running and and he at that day in Houston, it was um, 90 degrees and 85% humidity and got back had a glass of um, tea went back to the meeting had some more coffee and then as the afternoon session opened up I start to feel lightheaded and um next thing I know I'm looking up at the chandelier and there their they're shouting. Um,
55:07
Stroke cardiac arrests seizure and they're starting to pump on my chest. So they rushed me to the hospital where I had uh, a simultaneous workup for cardiac arrest and stroke.
55:20
And after um, I'll make the story short after uh, a hundred thousand dollar work up. It was determined. I had a faint
55:31
Because I was overdoing it.
55:33
So since then I now I try to get 7 to 8 hours sleep at night, right, but that's clearly the Bedrock
55:40
of
55:40
health. So so I increase I used to get 3 to 5 hours sleep a night now I get 7 to 9 if I can do it, uh cut back on on on coffee on caffeine and um, uh, I don't push myself to exercise like I used to have I'm feeling a little fatigued. I'm on an anti-hypertensive agent, but I actually don't take it every day because um for me it's better to have a pressure 125 to 135 and it's true for some of my patients if you've got some disease in your arteries, you may not want to have such a low blood pressure. So I would individualize it but in general, um, you want to take care of your body like I've learned and probably maybe you've learned over time. I'm learning. I mean, this is
56:26
very interesting. I've I tend to have low blood pressure it sort of runs in my family to have low blood pressure. Um,
56:33
I
56:34
Can definitely relate to the um hard driving, um ambition phenotype. I think it's it's worth people hearing this because its characteristic of a lot of people in high-intensity professions and I made the joke about Stanford faculty. But um, it's true. I think that if you're ambitious you tend to overdo a bit more that's something I'm certainly working on and I've um run a very busy life and learning to slow down prioritize sleep prioritize meditation. Non-sleep deep rest is something I've benefited from a lot journaling things of that sort. That really just kind of slow the pace. I think that um,
57:11
you know in the landscape of Health optimization we can often put ourselves into modes of excess in the other direction, um meaning doing so much to try and avoid
57:22
Issues with health that we end up creating issues with health, but yeah, certainly reducing caffeine intake and prioritizing sleep are key so that I appreciate that you shared that story. So if somebody has naturally low blood pressure.
57:33
And starts to feel a bit. Um, let's just say kind of sleepy or woozy in the afternoon. Would you recommend um that they obviously not take a a um pressure lowering drug, but that they add a bit of salt to their diet that they um, feel free to um, you know to
57:52
To exercise less. I'm a little bit confused. I I also love to run and and do resistance. Well, I would recommend they take their
57:58
blood pressure. So, um, you want to try to correlate any symptoms you're having with vital signs that modify, right? So take your blood pressure. If you're feeling faint if it's low, uh, 1 thing you can do uh easily is to hydrate. That was something else. I used to not drink much because I don't want to have to pee in the operating room.
58:17
I can imagine that'd be pretty uncomfortable. I don't want to be the patient that you're operating on when you have to go use the bathroom.
58:22
Yeah. So now and then uh, I'll reveal that I um had a kidney stone which is common among surgeons. Uh, this was a decade ago and since then, uh, I've hydrate all the time. So I hydrate to the point that my urine is crystal clear all the time
58:40
and that helps with some of the brain clarity.
58:43
So interesting, I've done a little bit of work with people in the Special Operations community and you know, I think people hear about them and they think oh, you know, what's what's the magic potion that they're taking? What are they doing? And they do a number of very interesting things. Um, but 1 of them is they really emphasize hydration.
58:59
That just like hydration water sometimes water with electrolytes if they're working in in in hot conditions. I just hydration hydration
59:06
hydration. I was skeptical um, and I used to dehydrate I felt better dehydrated and fit, you know, but um as I've matured, um, I think it's very very important. Um, and uh for you know for for your blood pressure for your General Health,
59:22
Uh, and for your kidneys Yeah, you mentioned sleep. Um, is there a relationship between sleep deprivation and stroke risk?
59:30
Uh, that's a great question. There's interestingly. Um Strokes occur more commonly during sleep.
59:38
It's not known why 1 theory is that it's related to circadian rhythms.
59:44
Um, I don't know if there's a relationship between sleep deprivation and and um and stroke.
59:52
I'd like to take a brief break and acknowledge 1 of our sponsors element element is an electrolyte drink that has everything you need. That means the electrolyte sodium magnesium and potassium in the correct amounts and ratios and nothing. You don't which means no sugar now, I and others on this podcast have talked about the critical importance of hydration for proper brain and body functioning even a slight degree of dehydration can diminish cognitive and physical performance. It's also important that you get adequate electrolytes the electrolytes sodium magnesium and potassium are critical for the functioning of all the cells in your body. Especially your neurons. Your nerve cells drinking element dissolved in water makes it very easy to ensure that you're getting adequate hydration and adequate electrolytes to make sure I'm getting proper amounts of hydration and electrolytes. I dissolve 1 packet of element in about 16 to 32 ounces of water when I wake up in the morning and I drink that basically first thing in the morning, I'll also drink element dissolved in water during any kind of physical exercise. I'm doing especially in hot days when I'm sweating a lot losing water and electrolytes. They have a bunch of different.
1:00:52
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1:01:52
Back into the spinal column and it worked terrifically. Well, I took no medication. I required no surgery and I eventually learned to correct some imbalances that have led me to not have that issue. Again. This is really remarkable in this chiropractor essentially. Um,
1:02:07
Saved me from surgery and and I'm forever grateful. So there I think there are excellent chiropractors out there. Um, but when I was a posto, uh living in San Francisco, I had a roommate I believe she was a neurology resident and she came back from the clinic at UCSF and she told me this story that a patient had come in who was experiencing some Hemi paralysis of the face that patient. I believe it was a young woman, um had gone for a a neck adjustment or head adjustment at a car with a dissection of her artery, right and something had happened and she had essentially a stroke.
1:02:41
Yes.
1:02:42
And so I I share both these stories to make very clear that I have nothing, um against chiropractors, but I think like any health practitioners they come in a range of talents. Um, uh, and this was really like for me, um an alarm and I decided at that point, I would never allow a chiropractor to adjust my neck.
1:03:01
I said, okay, you can you can make adjustments to my back. You can give me suggestions about exercises to do but how common are these um this uh, you said it's a hemi dissection. Um, it it's a dissection of an artery
1:03:12
either the uh vertebral artery in the back or the corded artery up closer, um in the front,
1:03:19
so no cutting when you say dissection, they're basically making an adjustment. Yeah.
1:03:23
Well what happens is um, and I I agree with I'm we're on the same page. I recommend patients if they're going to have chiropractor not to have manipulation of their neck because that's what occurs it's not common. But uh, I see it. We see it. What happens is the artery is damaged.
1:03:41
Um the manipulation of moving the bone and the soft tissues causes a tear in the wall of the artery.
1:03:50
And what and what occurs interestingly is that the blood that's usually in the the space the Lumen the middle of the artery gets into the wall and causes a false Lumen a false Passage.
1:04:04
and that
1:04:06
that blood in the wall pushes part of the wall into the the main artery obstructing flow.
1:04:13
And sometimes causing a clot to form that can be dislodged and go up to the brain yikes.
1:04:21
So
1:04:21
and there's no way to know whether or not this is going to happen. No, that's why I recommend not having uh neck manipulation by a chiropractor, even if it's rare. Um, it's it's so devastating when it occurs that uh, personally I I I would avoid that
1:04:38
um
1:04:39
Yes, I tell the chiropractor, uh, stay away from anything, um above the shoulders, please um, and then the back work has been beneficial again these exercises perhaps the most beneficial thing about it. Um, as long as we're there, I realize it's a bit of a niche condition, but what about hanging upside down? I had 1 of these inversion tables. I really enjoyed that thing. But then once I looked at my camera phone while I was hanging upside down and it looked like I was going to blow a gasket from all the vasculature in my forehead. Is it bad to hang upside down?
1:05:07
No evidence that it's bad. Oh good. Oh good. I maybe I'll get an inversion
1:05:11
table again. Um, as long as you don't stay there, of course you got some. Okay great. Um,
1:05:18
Would you
1:05:18
let your kids play football or rugby? That's a great question. I would not uh, that's my personal decision. I think there are a lot of benefits to um, children playing, uh football rugby like any sport. Uh, it's a team sport. A lot of good skills are learned. Um,
1:05:36
Besides the you know, just the the the physicality of it the coordination, uh, but being a team player and the socialization but uh, I think talking about tackle football. Um, uh, I think um the risk there's still risk. We're just learning about it and even um, high school players who who um, uh, many years ago were found to have multiple concussions are showing up when they when they're doing autopsies, uh, uh with some of this, uh, chronic traumatic and sephy. Um, I wanted to play football as a kid and I'm not that big. I mean I'm a big guy but um and my parents didn't let me which is fortunate because I mean, I'm sure I would have been would have been you know, put at risk for injuries not just head injuries other injuries. Um, my son who's a very good athlete he played 4 years of High School, uh baseball and soccer was at
1:06:36
Us to try out, uh for the quarterback position as senior year.
1:06:40
And we went out to try out but and he decided um, you know with my encouragement not not not to play. Did he go to Gunn High School? Yeah, he went to Menlo. Okay,
1:06:51
I went to gun. Our football team was at that time was bad enough that there was no incentive to play. What about soccer and heading the ball? I actually heard that can be problematic. Which to me at first when I heard that I I was like, no, there's no way I mean, the ball is so
1:07:03
light but is there any evidence that repeated, you know heading there is it's again, it's it's it's not uh, uh, incontrovertible but um, uh, there is some evidence that multiple headings can can cause some some concussions and some long-term injury. Um again, when I studied this in detail, um as the 49ers, uh, neurosurgeon back in the 90s, there was very little data, although there were some evidence even then that soccer players had a uh, High incidence, uh, and particularly female soccer players had a high incentive.
1:07:40
of of of concussion surprisingly
1:07:43
Um, but now there's much more evidence that head injuries and even heading the ball may lead to some you know, some some some injury.
1:07:52
I feel like if a sport is not your profession.
1:07:56
The risk benefit analysis is pretty clear. Like like like why box I understand. It's a great sport. There's a lot to learn there, um done a little bit of it in the past. But but unless you're going to get paid substantial amounts of money and maybe even then it's probably not worth it.
1:08:12
Well, I feel the same way. Um, it is different for professional athletes. I mean, this is their job. Um, you know, I remember talking with with Steve Young at 1 point about, you know, continuing to play or you know, finally decide to retire and uh, I was thinking what if you know, I was asked to retire as a neurosurgeon at the prime of my career
1:08:35
Um, you know, uh, it's your profession. It's your income. It's your you know, it's how you identify yourself. Um, you know, uh, your self-esteem is dependent on it your family may be put pressure on you as a professional athlete. Um, if you're not a professional athlete, I I think for me and this is my my own opinion individually, I think um, there's less of a controversy and what there's so many other sports which uh, uh benefit in the same way, um as as football or or boxing, um, why not? Why not, you know participate in those that's my feeling, but I know it's a controversial subject. Yeah,
1:09:21
maybe we can Circle back a little bit on a a fairly common scenario. Um,
1:09:26
You're in the attic and you're looking for something you stand up. Boom, you hit your head on a beam and you know kind of dizzy for a bit or a recently our a podcast team was on tour in Australia and the way that the the uh, shelf over the kitchen sink and our um, Airbnb was arranged. It was certain that everyone pretty much would hit their head hard on that thing at some point.
1:09:48
Does 1 need to worry about 1 kind of dizzy inducing head hit? Um
1:09:54
From everyday life, you know, I think a lot of people are kind of scared like do they do brain damage or is the The evolutionary adaptation which is the thick skull, um sufficient to you know, keep us safe in most cases.
1:10:06
I don't think you need to worry in general, especially if your symptoms resolve within a relatively short period of time such as
1:10:12
how long a day or 2.
1:10:15
Yeah, I mean, you know, even if you have a mild concussion and you recover within a day or 2, I don't think there's any need to worry or get a scan or uh, and and it's a common place occurrence.
1:10:26
Yeah, I think um, your answer will set a lot of Minds at ease because um people do worry. I mean it there's something so mysterious about the stuff that occurs inside the cranial Vault. We can't look to something we can't, you know, take our pulse. Um, there's just you know, it's so hard to know what's going on in there.
1:10:43
Well as you say that's why we developed very thick skulls to protect the the most important organ because after all the tissue
1:10:50
doesn't regenerate, um, at least not much of it. There are a few areas where there are where there are neurons that can replenish,
1:10:56
you know, I'm going to take um,
1:10:59
Issue with you at that because the the prior notion, of course was that once nerve cells in the brain die, they don't regenerate and for a long time. It was thought you don't produce any any new nerve cells any new stem cells in the brain.
1:11:15
Um, and we used to think after an injury, uh, or uh, a disease like a stroke when that tissue was damaged and you were paralyzed or you couldn't talk that there was no way to recover that those circuits were were dead. Uh, it turns out that is not true and we are learning that I think in recent years. Um, when I trained there was no hope to restore function in patients who had a
1:11:42
stroke traumatic brain injury spinal cord injury, uh, uh, and um other diseases, uh, ALS, Lou Garrick's disease, um Parkinson's disease now, we are learning that uh, there is hope
1:11:58
We know that stem cells do form in the adult brain. That's not controversial anymore. We know that other circuits can take over for circuits that were dead.
1:12:10
Um, and we know now and this is some of the work that we're doing with chronic stroke patients who we thought could not recover after 6 months at all. We know that there are ways of um, promoting, uh, regeneration or recovery of function. We're still working out the details of that.
1:12:29
But um, for instance we've done studies and this is still in um clinical trial phase.
1:12:38
With patients who are years out from a stroke. They've been through rehab?
1:12:43
uh, they've been through physical therapy and
1:12:47
90% or more of recovery after a stroke occurs in the first 6 months after that time, you know patients are not going to recover.
1:12:55
And now we are finding in some of our uh, early trials with patients that if you for instance put in stem cells into the brain, uh, or um, if you another treatment which was uh approved by the FDA the very first for chronic stroke if you put a stimulator on the vagus nerve in the neck.
1:13:17
and stimulate
1:13:19
coupled with
1:13:21
physical therapy
1:13:23
intensive Physical Therapy, you can improve arm function in those patients and our patients that we've treated in multiple trials. We're seeing early indications that patients years out from a stroke.
1:13:37
Can start to recover function in their arms in their legs in their speech?
1:13:42
And we don't know all the mechanisms, but the old notion that these circuits are dead is simply not true. They can be Resurrected.
1:13:52
And so, um, you know, this is part of the the the excitement about um, Discovery and um doing research and trying to translate into the clinical Arena.
1:14:03
Yeah, oftentimes this boils down to really critical of the moment decisions. I'll tell a story. Um, I won't reveal the the hospital or the the exact players involved but um some years ago an ex-girlfriend of mine, um who then was just somebody I was uh friends with um slash dating contacted me and said that her dad had had a stroke and I was um near that hospital. So I went um and spoke to the resident and the resident who was overseeing the case essentially said look at it's hopeless there's a huge necrotic piece of tissue in there. Um, the probability of any kind of quality of life is essentially zero my suggestion and I was there as as um, the resin made the suggestion would be to remove him from life support essentially and um, the other members of the family were like, oh my goodness, right? This is not a situation anyone wants to be in. Um, I made a couple of calls including to um, someone who's previously been a guest on this, uh,
1:15:02
Podcast who's highly qualified to know about this sort of thing. They asked a couple of questions about the location of the stroke which side of the brain it was on and said, um, keep him alive. There's a good chance that he'll have um some degree of recovery of function. So that's what they did and indeed, um while he lost some motor, um abilities, um, lost some speech abilities and has some disruption of affect where he'll sort of spontaneously laugh or cry from time to time. He has at least by my observation been able to enjoy substantial amounts of Life interacting with grandkids, um, enjoying holidays and actually took I was told some um some physical steps at some point with assistance with a Walker's gone done a lot of physical rehab, um, obviously, uh, really hard situation, but it told me that oftentimes when we think that All Is Lost not All Is Lost even in people in their 70s, right
1:15:57
it it has to do with plasticity.
1:15:59
And um, we all wish we were neonates or infants because um the body including the brain is so plastic that's the ability to regenerate tissue and circuits and recover. So if an infant has a stroke and is paralyzed on 1 side, usually they can make an excellent. If not complete recovery. Um, this is the as I recall from my
1:16:23
undergraduate years the Kenner principle, if you're going to have a brain injury have it early in life exactly,
1:16:28
right? So, um, I mean you notice this too when I cut myself now it can take a week for that cut to heal when my granddaughter who's 6 years old cuts herself the next day it's totally healed. So
1:16:40
yeah little kids are like salamanders, right? They almost it's all by the way. That was a biology joke, they're not like salamanders that but um, salamanders can re uh, regenerate entire limbs by the maintenance of a small stem cell population at the at the tip of the the limb Bud. Um, or what would be the limb Bud. Um, and it is remarkable how
1:16:59
Kids can regenerate without a scar they can oftentimes they can't grow an entire hand back but it's kind of striking how much plasticity
1:17:07
there is and that's what we're trying to develop are new ways of promoting plasticity in the adult brain as an example. So we think stem cells injected through various mechanisms stimulation of the brain or the vagal nerve is an example.
1:17:24
can promote plasticity in in a sense we think what's happening is um that these methods
1:17:32
Can turn the adult brain into an infant brain in some ways, where are the stem cells coming from in these experiments? It depends. Um, there are different sources. So, um some of the studies I've done previously with other companies, uh, they made the stem cells either from uh, bone marrow donors.
1:17:53
So they were mankal or uh, another group made the cells from uh from fetal, uh neural tissue. Okay. So just to orient people inside
1:18:05
the bone. You have the marrow most people know that um, because they've ordered it at a restaurant, um cow marrow that is um, uh typically, um, the cells within the marrow, um contain as I recall a hemopet potential blood cells, you know cells that can become blood cells or other things and if taken out put into a petri dish and given the appropriate factors,
1:18:31
You can drive the fate of those stem cells to be say neurons or cardiac cells and then you're taking those cells and you're injecting them into the brains of patients in the hopes that they will re uh become neural cells neurons that will incorporate into the circuitry. Actually. That was the initial notion 20 years
1:18:49
ago when we started doing this was that these cells you put in, uh,
1:18:54
Become these exogenous sells you inject become neurons and astrocytes and illegal dendrocytes all the cells in the brain and that the neurons reconstitute circuits. That is not how they work.
1:19:08
The way they work.
1:19:10
And this is why it may not uh matter what particular type of stem cell you put in.
1:19:16
The way they work primarily is by secreting very powerful proteins molecules growth factors that promote native
1:19:25
recovery.
1:19:26
So they promote.
1:19:28
Angiogenesis, they promote native neurogenesis endogenous gliogenesis synaptogenesis, but the main benefit may be that they modulate the immune system. That's what we're finding.
1:19:41
So by modulating somehow the immune system in the brain.
1:19:46
They are able to induce plasticity and recover function interesting. I I'm tempted here to weave in the the stories
1:19:53
that date back to the 90s, but that we see more and more of mostly studies in rodents. But a few in humans showing that there are dormant stem cell populations in certain compartments of the brain the dentate gyrus of the hippocampus the olfactory bulb Etc that upon
1:20:09
Hyperoxygenation or increasing blood flow to the brain largely by virtue of exercise but also sometimes by way of engaging in learning tasks and exercise that you can basically cause the release of stem cells that normally would lie dormant is that um literature reason enough to suggest that people who've had a stroke, um, continue to move their body to walk get exercise. Maybe do resistance training maybe even some skill related training.
1:20:37
Yes. There's a lot of evidence that um activity Physical Therapy even forced activity, um is very beneficial and it's not just um, stimulating endogenous stem cells in the brain, but it's multiple mechanisms. Uh, it's recruiting, uh circuits that were not involved before for instance Studies have been done on stroke patients who make a recovery show that um, not only is the side of the stroke.
1:21:08
improving in some cases but the other side of the brain
1:21:13
Is showing increased activity.
1:21:16
So circuits on the other side of the brain may be contributing to the recovery on the the side of the stroke brain. So it's much more complex than we thought it was.
1:21:27
Years ago I um developed an affection for a literature. It wasn't a very prominent literature. Um, but I found it really interesting. Um is the work of a guy named Timothy shallard and um, Teresa Jones I yeah, I know you familiar with this.
1:21:42
Yeah, we almost recruited him to to to our department.
1:21:44
Yeah, the sort of overarching theme of this literature was it was animal work? Um, but I think some of it might have been translated to humans, which was that for instance. If somebody has damage on 1 side of the brain, uh, because of the way the circuits are organized and of course, you know this better than anyone Gary but that 1 might experience deficits in limb movement on the opposite side and that the tendency for somebody like that is to then over rely on the intact limbs. Um, essentially lean on the the intact Limbs and the approach that they took to try and uh recover function was really interesting. They had these animals and I think eventually there was some human work done. I could be mistaken, um sort of uh tie up the
1:22:27
The more active uninjured arm or leg or hand such that they then had had to rely on the non-dominant or let's just call it injured sometimes even flaccid paralysis limb. And in that way, they could generate a lot of plasticity that normally would escape the patient especially in the days and weeks following the injury just forcing movement, uh, or forcing the attempt to move of the injured pathway. I find this literature to be so striking and maybe 1 that uh should deserve more attention. Yeah,
1:22:57
it's called constraint therapy. And um, not only has it been shown in animal studies pre-clinical but it's been shown in some uh, clinical studies of patients with stroke. In fact 1 of the trials. We did with transplanting stem cells into the brain included restraining the good limb to force use of the other limb.
1:23:20
So there's um some very intriguing data suggesting that that's important. However, some of the
1:23:27
animal studies also suggest that you may have to wait a time if you force use of the uh involved limb too soon, it can be detrimental to the recovery. I see so there may be a a a an important temporal Factor there in terms of the timing of when you do that.
1:23:45
Is there anything that people can do or take?
1:23:50
For neuro protection after an injury to essentially try and rescue neurons that would otherwise die.
1:23:56
Right? So this is a a very interesting subject. Um back in the late 1980s 1990s. A lot of emphasis was placed on trying to protect the brain against acute stroke.
1:24:10
different pharmacologic agents were tried, um, probably um,
1:24:17
A thousand different drugs were tried, which blocked?
1:24:22
Uh the pathway leading to cell death. So interestingly when you deprive the the brain and the neurons of oxygen and glucose they don't die immediately.
1:24:33
And it takes some time and it's actually an active process. So the release
1:24:40
of
1:24:41
these excitatory amino acids occurs. So normally as you know, glutamate aart are important neurotransmitters in the brain and you need them to function, but after a stroke when there's a deprivation of oxygen and glucose and a mismatch between the metabolism and the supply of oxygen and glucose.
1:25:02
For some reason there's a release of these excitatory amino acids, like glutamate and that causes an influx of calcium into the neurons, which is the final common Pathway to dying.
1:25:18
And then there are other Pathways that can that lead to release of free radicals and uh, which are more damaging and those can cause another type of cell death called apoptotic cell death. That's a a a cell death that are requires proteins. This is and then uh with reperfusion, um, say the artery opens up, then you got a lot of inflammation. So these pharmacological treatments as I say a thousand of them were tried, um, and they were found to be very effective in pre-clinical stroke models so we could cure stroke in the lab my lab studied this for probably 15 years and um, you know, there was no doubt we could cure stroke if we got the drugs on board even after the stroke.
1:26:06
um within a few hours
1:26:08
But it never was able to be translated to the clinical Arena except for 1 case. So besides drugs that were tried.
1:26:19
Um, another method of protecting the brain was tried called mild hypothermia.
1:26:25
And that was a process of reducing the brain temperature and body temperature.
1:26:31
Just a few degrees from 37 degrees centigrade to 33.
1:26:37
And we were 1 of the first to to show um, that that was protective even after the stroke in animals.
1:26:44
Um, my understanding is that when you cool neural tissue, you quiet. It's electrical activity. In fact, this is a common, um tool for experimentation in Neuroscience Laboratories, you know, you want to shut down a a brain area a transiently you you cool it down,
1:27:00
right? And in fact deep hypothermia has a profound effect on shutting down the metabolism. So that's why when a someone particularly kids fall into a frozen pond with with ice cold water they can survive there for half an hour.
1:27:17
Uh and make a complete recovery because their body temperature is dropped down to very low like 20 degrees centigrade. But this is less. This is just a few degrees. So the amount there is a slight decrease in the metabolic activity, but that does not account for all the protection. It's due to the fact that hypothermia mild hypothermia blocks many of those detrimental Pathways it blocks.
1:27:42
Partly the release of those excited to amino acids glutamate. It blocks the calcium influx. It blocks the inflammation.
1:27:50
Uh, and so, um, that's probably why it works. So well even blocks that other pathway of programmed cell death, um because it hits all these Pathways it's multifactorial. It's very effective. And in fact, it was finally shown in the early 2000s in prospective randomized studies that 1 type of stroke actually 2 types. I should say 2 types of stroke.
1:28:18
Are benefited by cooling the brain quickly 1 is cardiac arrest from ventricular fibrillation.
1:28:24
And prospective studies which were published in 2002 showed that if you uh, cool patients who have cardiac arrest and then a resuscitated out in the field down to between 32 and 34 degrees Centigrade from 37.
1:28:41
Much better outcomes neurologically, that's from Global. Eshka. That's the no blood getting to the brain briefly and the other area where it's been shown to have um, better outcomes is in neonatal what's called hypoxic, esmic injury. Those are neonates who have lack of blood flow for some reason the brain when they're when they're born and if you cool them, it's been shown in studies up to 10 years later that the they have better cognitive outcomes.
1:29:11
So for cardiac arrest in in uh in the mid 2000s, uh, I think it was 2003.
1:29:19
the American Heart Association
1:29:23
Determined it was a standard of care a guideline that you had to cool patients after cardiac arrest. Yes. How was the cooling done in the experiments that you were involved in? Yeah. So there are many ways to do it. But in the animal models, you can just cool them with a a cooling blanket actually in people. Uh, we got very interested in this. In fact when I saw in the laboratory that it was so effective and and that we could cure it, you know Mouse and and rats Stroke by cooling. I started cooling my patients in the operating room. Um, because I I felt you know, even if it hadn't been proven in in in in patients that you know, it was so effective. It's the gold standard now actually for neuro for neuro protection against stroke in the in the laboratory.
1:30:13
So back in um, the 1990s. I started cooling all of my patients. We started by cooling them by putting um packing them in ice and putting alcohol on them. But uh, the operating room staff appropriately didn't like that because because alcohol is inflammable. So then we started using cooling blankets.
1:30:36
And then a number of companies, um started developing cooling catheters and I work with several of these so you can actually cool very quickly. Uh, if you put a catheter in the uh into a a a a vessel say in the groin and um, Infuse cold saline, which doesn't get into the into the circulation but it cools the blood and the cool blood then circulates, um other ways of cooling are to putting on um, um, special devices which cool quickly and that's what's used now are are external devices people are working on cooling just the head with helmets. Um, so it's still an active field of of Investigation for stroke and also for cardiac arrest actually, it has not been proven in well-designed prospective trials that it works for.
1:31:31
Garden variety focal stroke. It works for cardiac arrest where there's Global lack of blood flow to the brain like when the heart stops.
1:31:41
It hasn't been proven yet for the kind of stroke. We've been talking about where there's a single blocked
1:31:46
artery to the brain. So interesting. I mean a lot of times on this podcast we talk about the critical need for body temperature to drop by 1 to 3 degrees to get into deep sleep. We had Craig heler our colleague from the biology department at Stanford on the podcast where we talked about some of the Palmer Cooling and um, essentially cooling the um Souls of the feet the palms of the hands in the upper part of the face as a way to more rapidly reduce core body temperature. Um, I think these are fascinating areas for exploration. Um,
1:32:15
That obviously have clinical applications. But it but also you would imagine for some of the things we're talking about before like just to um provide a bit of neurop protection after a head hit or provide a bit of neurop protection perhaps even as it relates to aging, you know, spending a little bit of time maybe 10 minutes a day, you know.
1:32:35
It's not badly hypothermic. Please people but slightly hypothermic and then bringing the body temperature back
1:32:40
up. Yeah, I mean I wouldn't recommend if you have a head injury or or or a TIA to stick your head in a in a snowbank.
1:32:49
But um, even with traumatic brain injury severe not just concussion, but severe TBI traumatic brain injury, um studies were done looking at cooling hypothermia, and this called mild hypothermia because it's just a few degrees.
1:33:03
And the studies were very suggestive but uh didn't get to the point that it was proven. Um, although certain subgroups who were cooled quickly seemed to do better.
1:33:14
So I I think it's a subject that's still being studied. Um, and as I say it's easy for us to do in the operating room. You don't want to cool too much because that can then interfere with um other um, metabolic functions and clotting parameters and they're uh it C can cause increased infection if you go too low for too long, but um, I still um, uh, let my patients cool just a few degrees and we've had some anecdotal cases where where patients have had um, uh problems. Um, and um because we cool them we think it it it made a benefit. For instance. We had 1 patient who we hadn't even done. Uh, I was getting ready to do a bypass to sew a scalp artery to a brain artery, but we hadn't even um, uh, I think made the the the the skin incision and the patient had a cardiac arrest
1:34:10
So we um.
1:34:12
Uh, and and it'll ask it for a long time. So we were pumping on the chest, uh couldn't restore function and it was uh way outside the uh amount of time that you would have expected a good recovery, but the patient had been cooled down to 33 degrees before we by the time it had happened.
1:34:31
And um and then we finally, uh got the heart started. We ended up putting some uh, restoring flow through catheters and a and a heart lung machine and remarkably the chime made a complete recovery. So anecdotal but cases like that, um suggest maybe cooling. Um, even a few degrees has a protective effect on the brain. Um, we certainly know it. It's true for cardiac arrest and global eske.
1:34:59
What are your thoughts on platelet rich plasma PRP these days we hear so much about PRP. I think it's FDA approved for certain things right people will get um blood drawn they'll
1:35:10
um spin down platelets and then put in platelet rich plasma. Um,
1:35:16
A few years ago people were making claims out there about PRP containing stem cells, uh, just for the record my understanding. I'm sure someone will argue with me online they always do but my understanding is that PRP contains very few if any stem cells, um, and that it's not legal to assert that PRP is stem cell therapy, but PRP seems to be something that after an injury or in anticipation of a surgery people are trying to do more and more because they can go drop a few thousand dollars and I don't know get this infusion of PRP does it does it work to help recover brain tissue or preserve brain tissue? Is there any evidence of that whatsoever?
1:35:53
I'm not an expert on on platelet rich, um, you know, um plasma but um my reading of the literature, uh, cursorily, uh, suggests, there's not hard evidence that it's beneficial. I think 1 has to be a little careful for instance. Um, I still um get um emails
1:36:15
Uh, you know every few weeks from people saying, uh, I've had a stroke or I've had a head injury and uh, should I go to uh, Russia or India or Mexico and get um stem cell therapy? Yeah. This is a big topic area and and you may have discussed it in another podcast.
1:36:37
I have not I'll do a solo episode on stem cells and what they are and what they aren't I I just will just sorry I didn't uh interrupt but I'm aware of a clinic in Florida that was injecting stem cells into the eyes of patients with macular degeneration and some other eye issues and those patients rapidly went blind. I was going to bring that up and that's what led the FDA to really clamp down on stem cell clinics in the US,
1:36:58
although they haven't clamped in on those type clinics as well as they should but I um, I tell patients know if you go out of the country, uh often you don't know what you're getting if there's not a an equivalent of an FDA, which is overseeing it. Um,
1:37:14
you don't know whether these cell where they come from. Sometimes they're not published literature. Um, you don't know um where they're derived we've seen cases of patients going elsewhere getting injections into the brain or the spinal cord and developing tumors or other problems. So I discourage that and I was going to bring up even in this country, um these clinics and that was published, um a number of years ago that clinic in Florida. Um,
1:37:43
Those patients had macular degeneration and they were losing their sight but they could still see to some extent they had their own adapost tissue taken. They sorted it for certain, uh stem cells stem cells and it was re-injected into the into the I should have been safe write their own cells even and as as you say several of them went blind irreversibly irreversibly. So, um, I think this is very important to highlight the the dangers of of stem cell therapy in general. There's a lot of Hope for it. I mean, we're engaged we're just finishing a a trial of first in human trial at Stanford using cells we developed in my lab 20 years ago. It took us 20 years to prove that. They were safe effective didn't cause tumors and the study is looking very promising. It's a phase 1 study and we we're making uh plans to do a phase 2 study with control patients, which you always want to do. Uh, but despite the hope
1:38:43
Um, there is still a lot of hype and I think it's very important to to be careful about getting therapies that are not proven.
1:38:52
Yeah, and uh while we wouldn't want anyone to take any kind of unnecessary risk, you know to me anyway, this goes back to the beginning of our of our conversation that there's something very different about a knee from the brain right. I'm not saying go get stem cells injected into your knee, but should you be the sort of person that
1:39:10
Wants to do that because that you feel that's within your rights, you know again, I don't tell people what to do and you go to a clinic they get stem cells or I don't know they they take stem cells from some source and put them into your knee. I mean that's a very different um situation than injecting into the brain respond.
1:39:26
You know, what some of the approaches um to treat diseases of the brain or injuries to the brain are not injecting directly into the brain. They're injecting intravenously or in arterial threading a catheter up as we discussed in injecting in the brain those cells. It turns out don't even get into the brain.
1:39:44
Um, and the idea is that uh in some of the better studies that that have been done, uh in animals that they work by modulating the immune system systemically those cells get trapped in the lung and the spleen which people describe as bioreactors and modulate the immune system, which does make some sense as I say, we we think 1 of The Main benefits of these stem cells is that they modulate the immune system and that helps with plasticity in the brain, but even intravenous delivery can be can be dangerous.
1:40:21
To the brain.
1:40:22
Yeah, this is an area that uh, we will spend a lot more time on during this podcast. Um,
1:40:29
Despite what you just said. I think the the data I've seen from your laboratory. And as you you told me there's a trial that's finishing up now. Um
1:40:37
That uh features those data or that uh is where those data arrive from rather, um are really impressive. I mean some people who were largely immobile or aphasic they couldn't speak, um in some cases are able to speak or move and that's really remarkable. It's really exciting. So, I think that that the future of stem cells and stroke therapy, um is pretty pretty bright at least from where I sit. Yeah, we don't want to oversell this um,
1:41:04
but uh, some of the uh results in certain patients are remarkable, I mean the patients and their families say it's changed their lives if you see them before and after it's almost like a miracle others are not as impressive but uh so far in our trial, uh, and we've treated 17 of the 18, uh intended patients, uh,
1:41:28
Almost all the patients have recovered to some extent and many of them have improved, um in a meaningful way if you use certain scales. So again, we want to be cautious we're going to do a prospective randomized blinded controlled study. Uh, and that's the way it should be done. And um, if that's positive it would lead to a a a a phase 3, um larger study again blinded controlled and if that's positive then it would lead to commercialization FDA approval. Um, it's a long process. I've spent 23 years and more than 40
1:42:11
6 million dollars in Grants and philanthropy, um getting it to this stage. Wow. Yeah.
1:42:16
Wow.
1:42:18
That's that's a lot of time and a lot of money.
1:42:21
Amazing. That's the way science and and and translation to clinical medicine is um, I would be remiss if I didn't
1:42:30
ask, you know, what are some of the things that you think could accelerate that process or is that just the slow iterative process that is science and medicine. I mean for instance if there was um, 5 times as much money, um, would the science progress at you know, 5 times the rate probably not. Um,
1:42:46
no but money money is a factor. Um, it's not the only Factor, uh, the FDA is
1:42:53
Appropriately very cautious. I think uh other countries the equivalent of the FDA, uh moves things along a little quicker especially for therapies where there's no no, no other treatment.
1:43:05
um
1:43:06
Uh, so, uh, I think those factors are are important. Um and would accelerate it. I think greater collaboration with industry and promoting more academic industry kinds of um, relationships would help because uh, the government agencies, uh, do not uh provide enough money to uh, do the final stage, you know, there's called this Valley of Death where you get initial, uh, encouraging, uh, data even clinically, but you can't move the hurdle to get it into FDA approval, um, because of uh of money in some cases I've seen as an example, uh, a number of very good stem cell therapies, um not make it because the companies went bankrupt the board of directors of the company felt the results were good, but not good enough and they pulled the funding.
1:44:01
Yeah.
1:44:02
So, uh, this is a whole area, which I was not well well informed of until I got into this, um of how you you know, move through the FDA and how you um, you know work with industry. Uh, I haven't formed a company yet, but I'm gonna have to because for the next trial this trial I was fortunate to get a grant from serum California Institute for regenerative Medicine of 12 million dollars
1:44:28
taxpayer dollars, exactly great use of taxpayer money putting it to really Forward Thinking research,
1:44:33
but the next trial and our results are good enough that we probably will only need if we do a statistical power analysis 69 patients initially. We thought we'd need 170 patients, but the results keep getting better and better so now, uh, it seems we would only need uh, uh, uh, uh about 69 patients that will cost at least 45 million.
1:45:00
Um, and that's the trials get larger even more. So, uh, yeah, we need to to figure out a better way to allocate money to to make these advances sounds like um a company
1:45:11
or some role of industry is going to be necessary a
1:45:14
um, well, you might be interested in investing right? I mean, well that the um, the this podcast
1:45:20
is always available free the standard human Lab podcast our premium channel, um, actually generates, uh money we do, uh, ask me anything things and things of that sort. We have donors that have come in for a dollar match and we do philanthropy to Laboratories at Stanford Salk Institute Columbia University. We've already done that we're going to do more of this. Well, I was I was being faced. No listen, we can explore it 1 of the 1 of the guidelines is that we fund research on humans exclusively. Um, so we could talk about that the um, uh former colleague of ours at Stanford. Um once told me that the joke, um, we'll see if I get in trouble for this joke, um, which is that there are 2 kinds of Stanford faculty Stanford faculty with company.
1:45:59
And Stanford faculty with successful companies. So, um, we'll see we'll see we'll see what comes down the pike from that but you know, I mean many of the Technologies and and discoveries that have been made at Stanford have spun off into um, you know, there are these little companies like, you know, Genentech and you know other companies like that that um are not strictly Stanford relations, but of course other universities too, but you know universities are where the basic research is done and then somebody has to implement
1:46:24
those Stanford's getting much better when I came to Stanford in 1974. Um, it was uh, the medical center was more like an NIH of the West and there was not a lot of uh, clinical Excellence except for cardiac surgery Norm someway and radiation oncology. Uh, Henry Kaplan who had developed the first radiation U method for treating lymphoma. Uh, and we were great at making basic discoveries not very good at translating them. But over, you know, the last what 50 years Stanford is
1:46:59
Gotten much better at uh, translating them, um, uh into you know clinical therapies, uh, and even doing some of that work at Stafford not farming it out to other other places. So I think that's another area that we need to we need to encourage. Well the proximity
1:47:16
to um, big Tech. Um,
1:47:19
Is uh sort of built into the fabric of of the Bay Area now, there's just no escaping that and I think uh overall, um, you know, it's not without its sometimes issues, but overall, I think it's a really good thing, um facilitates or the most rapid possible flow between basic science Discovery and um implementation at at large. Um,
1:47:41
I want to make sure that we cover just a little bit about vagal stimulation. A lot of listeners of this podcast are familiar with the vagus nervous this very extensive pathway connecting brain and body in both directions. Um, the common idea out there is that the vagus is associated with calming because it's a in the parasympathetic arm or the autonomic nervous system the so-called rest and digest pathway, but I happen to know and I'm sure you know from experimentation and from Clinical work that oftentimes vagal stimulation is a way of bringing say depressed patients up to more alertness that vagal stimulation is not always about calming it's can be about alerting the brain. Um, we're making the brain more alert. Um, so what sorts of vagal stimulation are you doing? Um, given that the vagal pathway is so um extensive, you know, like like which branch of the vagus do you stimulate there's goes around the ear. It's in the neck it goes down through the gut. I mean we're talking basically about a super high way of I mean, it kind of reminds me of the Austin freeway system. If you ever driven in Austin, it's like the freeways go and
1:48:41
Very much Direction. So whenever I'm there, I'm like the freeway system here is kind of like the Vegas so which um Avenue
1:48:47
do you stimulate in order to get a desired effect? Right? Well for stroke and as as I alluded to um vagal nerve stimulation coupled with physical therapy physical activity, very intensive was the very first FDA approved treatment for chronic stroke patients that was approved in uh, 2021 3 years ago.
1:49:10
And it was shown in the study that compared with um, non- stimulation in other words putting the stimulator but not not stimulating and doing the therapy that patients did better. It was a modest Improvement but felt to be uh meaningful and it was shown to be effective at 90 days only 3 months now recently at the last International stroke meeting last, uh, this past februari, uh, it was presented and I don't I don't know if it's been published yet that those results hold up for a for a uh up to a year.
1:49:50
So, um the way it works presumably is that you stimulate the entire vagus nerve in the neck.
1:49:57
And it's not the peripheral effects on the heart or the other autonomic organs.
1:50:03
Where it's working, it's stimulation that goes back to the brain.
1:50:08
Right because when you stimulate a nerve it doesn't go in 1 Direction and that's probably how it works for depression. Also, not a systemic but and the vagus has lots of connection with brain functions, right?
1:50:21
Um, and so that's it's not completely clear which areas are being stimulated to recover from stroke or or improved depression, but its brain stimulation that somehow again resurrect circuits or induces plasticity in circuits. Uh, again, it's it's a it's something that um, we're learning about and uh, I think not just vagal nerve stimulation, but stimulation of the brain is becoming a very important, uh, Innovative treatment for many brain
1:50:56
diseases and injuries is the vagal stimulation. Uh, is it invasive or can you
1:51:03
use an external stimulator? It's invasive you have to do an operation. It's low risk, um, very few side effects. Occasionally. There are some uh, it can cause some problems with swallowing which are usually temporary right because the vagal nerve, um, the recurrent vagal nerve
1:51:21
supplies the the larynx the vocal cord
1:51:25
But um, so it's an implanted stimulator.
1:51:29
But the stimulation could be turned on and off with an external um magnet.
1:51:34
device incredible
1:51:37
Gary uh, Dr. Steinberg, I want to thank you, um for several things first of all, uh for coming here today to share with us, um, right up until the point we hit, uh, hot mics meaning we we started recording. Uh, you were getting calls about patience. I know you're still in the operating room. You were our department chair for more than 2 decades 25 25 years. Thank you for that. Um, uh and you know still just so active in this area doing Cutting Edge research and stem cells and so much more. Um, so as an extremely busy person who has many important duties you are literally a brain surgeon, um to take the time out of your schedule to come here and share with us all this information about how to keep our brain healthy the relationship between alcohol and nicotine fortunately caffeine is not on the list, but don't overdo. It folks, um neurop protection the discussion about TBI something we've never discussed on this podcast.
1:52:31
Um transient is schema attacks and just
1:52:34
A really vast survey of things that concern a lot of people and that also now having uh heard what you've shared also.
1:52:44
It puts them in a position now to empower themselves to take some agency over their brain health, which is something that I think most people really fear that this thing inside our skulls is outside the reach of our efforts to try and maintain health and clearly you've um explained how that is not the case and there are things we can do to both protect ourselves and to overcome challenges. Should they arise so on behalf of myself and and all the listeners and viewers. I just want to say thank you so much and hopefully as these trials, um continue to develop, um, you'll come back and update us on the progress Andrew. It's been a real pleasure. Thank you for inviting me. Thank you for joining me for today's discussion with Dr. Gary Steinberg to learn more about the research in the Steinberg laboratory and Clinic. Please refer to our show note captions. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us in addition. Please follow the podcast on both Spotify and apple by clicking the follow Tab and you can leave us up to a 5-star review, please also check out the sponsors mentioned at the beginning and throughout today.
1:53:44
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