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

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life 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 our brain which is a scientific term explaining how blood flow to the brain supplies oxygen and critical nutrients to our neurons our 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 discuss 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 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 cerebrovascular 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 eight sleep eight sleep makes Smart mattress covers with cooling Heating and sleep tracking capacity now I've spoken many times before on this podcast about the fact that sleep is the critical foundation for

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sure you click the follow tab on Spotify Andor apple and on both Spotify and apple you can also leave us up to a five-star review and now for my discussion with Dr Gary Steinberg Dr Gary Steinberg welcome thank you Andrew pleasure to be here 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 consequen of Aging sometimes as a consequence of certain activities maybe you could just explain for us right off the bat what is a stroke what is

an aneurism 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 sure so a stroke is like a heart attack of the brain uh it involves disruption of blood flow to the brain either in the form of a blocked vessel 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 cored artery and dislodging and blocking blood flow to the brain about 133% are caused by a hemorrhage Bur thing of a blood vessel 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 how do we know if we have clots residing in our body that could be dislodged um I know that some people

when they fly we wear 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 may heterozygote for um Factor five lien which is a clotting Factor um heterozygote folks means I have one 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 who are homozygous mutants for five lien 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 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 mut ated or uh represented that predisposed to to clots and those clots can occur on the arterial side or the Venus side

the arterial side is what generally causes a stroke an es schic stroke uh on the Venus 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 Venus side and that can cause uh something like a uh deep vein thrombosis uh which is not good because it can travel to the lung and cause a pulmonary embolis that generally on the Venus side does not go to the brain oh good in my case that unfortunate exactly uh you can

develop some Venus problems in the brain which can cause a Venus type type stroke that's much less common and the way that causes a stroke is not lack of blood flow being delivered to the brain but 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 of of a vessel what are

some things that impact clotting and or excessive bleeding um my understanding is these Factor five light in mutations are one 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 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 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 some Interruption um to the to the body um like a bruise um it would be a much worse um type of bleed uh so aspirin is a type of antiplatelet agent that thins the 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 anticoagulants are another type uh they're they're called uh they're known as kumin warin elquist there's lots of lots of new agents um and uh they're often taken orally

or can be given intravenously uh heprin another one uh again they thin the blood so they would uh put someone at somewhat increased risk for Hemorrhage 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 uh it turns out and they were heavily estrogen um dominated rather than progesterone um they did and they still to some extent increased the risk of developing clouds so women back in the 70s who took oral contraceptives and smoked had a very very high incidence

of developing uh clots and and Es schic strokes and clots elsewhere in the body the newer Generations 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 estrogens or or progesterone systemically 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 so smoking is a very uh high risk factor for developing uh clots um which can lead to Strokes heart attacks peripheral vascular disease um High lipids is another so when people have high 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 cholest stro 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 interesting and then hypertension is another uh risk factor for for developing uh 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 increases the stroke risk or is it nicotine itself it's not just nicotine nicotine is one of the factors but it's the other uh products that are produced by by smoking that 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 yes the the incidence of stroke is actually decreasing um it may be in part due to decreased

smoking but it also is in part due to 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 obesity those are risk factors also for for for developing strokes and as well as heart attack 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 brain

um given the enormous amounts of blood and glucose that the uh the brain requires to function normally yeah 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 represents only 2% of the body weight yet it draws 15% of the total blood flow and remarkably it consumes 20% of the body's oxygen 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 in uh in the landscape of the brain yeah it's it's clear that um of all the tissues in the body if you had to pick one tissue to remove one you know cubic millimeter of that tissue that your brain and probably the neural retina would be your your least uh favorite um choice just given the deficits that can result right and of course the brain also is what makes us human right speaking

of which if we take a little departure into uh neurosurgery itself your your specialty um of all the years of of doing brain surgery um can you recall maybe one 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 a given brain area or removing a given brain area or or something of that sort I 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 consider 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 one of the more um profound um Insight stimulating moments um from doing brain surgery they're I mean every every patient is different so I'm always learning and 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 ago uh I had a p patient who had a vascular malformation which was located uh we thought right in her speech area 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 of where the speech area is we can map it out on an MR scan 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 neur neuronal activity uh when the speech area the language area is stimulated by talking 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 so we had 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 with her awake so we took what we did was we sedate the patient we don't put a tube down and induce

general anesthesia we numb up the scalp we take off a piece of bone after cutting the scalp open the membrane covering the brain called the dura and then we allow the patient to wake up more from the sedation and then what I did on this particular patient was to use a uh tiny stimulator a little probe and I can stimulate areas of her cortex with her awake and see if the stimulation impairs her ability to speak or understand language and quite surprisingly there uh was no activity in the corridor that I chose sometimes when we

see uh an area that is involved with speech that's eloquent we have to choose a different pathway way to get to the underlying vascular problem and so that's what we did in this case 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 millim so that I think is the gentlest way other times I've been surprised um uh about brain function is uh operating deep in the brain there's a part of the brain called the brain stem which you know well it's a small area that connects the thalmus those are the signals coming from the cortex go through the thalmus to get down to the face arm and leg to move the muscles and all the sensory information which comes from the arms and the legs and face goes through the brain stem up

to the thalmus and then to the cortex in this area although it's very small are contained uh very closely packed fiber tracks and nuclei those are the cell bodies for very important neurons and when I trained back in the 80s we never operated in that area because we couldn't do it safely with developments in computer technology and imaging and anesthesia we can now 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 two

vascular malformations um and they're not big I mean they measure between 8 mm and a centimeter but they can wreak havoc in the brain stem because it's such high price real estate and these had bled but I found a safe Corridor 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 that amazing yeah it's 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 I've 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 neurosurgery is becoming much less invasive and this is something that I really tried to push when I was a chair of the department for 25 years at Stanford um so

minimally invasive techniques include operating through the vessels right so now my I don't do this myself but my colleagues some of whom are neurosurgeons some are Interventional radiologist they can go through the groin in the femoral artery or through the radial artery they can thread a catheter backwards into the brain from the groin they can go up into the aorta up into the kateed artery 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 thrombogenic coils there or

new devices 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 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 one of my colleagues actually and this uses uh beams of radiation gamma knife uses a Cobalt Source multiple uh sources of cobalt 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 and the advantage of this is you don't have to open the skull you focus it on a very small area and you can eliminate um vascular malformations called arterovenous malformations tumors you can even use it for some pain conditions like trigeminal neuralgia it's not risk-free because even though radi ation is not is doesn't require opening the skull it Stills a form of energy that's damaging that that's how it works it causes for the avms it gradually clots 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 when I trained we used to shave the whole head we would open a huge area of the of the skull now we operate through tiny a 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 wow 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 um on areas of the brain we're using that to treat uh essential tremor MH or um uh Parkinson's disease um it's starting to be used for treating tumors so these are all advances that um were not present when 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 and stimulate the brain so that uh was first used for treating Parkinson's disease

very effective for medically intractable Parkinson's it's used to treat chronic pain recently it was shown to be beneficial uh for epilepsy in fact the two 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 a very difficult um epilepsy so this I think is going to be the future is minim more and more minimally invasive in fact we're using some of these techniques to even treat um psychiatric disorders like depression obsessive compulsive Behavior incredible I

should have asked this earlier but um Tia is transient es schic 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 Fusion 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 es schic attacks and is there anything that people can take for transient es schic attacks and I of course would love for you to inform us uh what a transient esic attack is right

so a transient esic attack or Tia is a reversible stroke uh it results in a temporary loss of function such as uh inability to move partial paralysis or complete paralysis but then it resolves uh inability to speak visual problems double vision blurred vision loss of vision uh it can cause uh slurred speech uh or difficulty understanding language imbalance problems walking even cognitive problems so it can vary depending on what part of the brain it affects in the past it was defined has a neurologic deficit due to lack of blood flow that lasted less than 24

hours but 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 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 in some cases a hemr 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 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 observe um spinal strokes and what are some of the symptoms of spinal stroke 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 and by two so for those listening sorry it would be the um sorry on the stomach side of of the body yeah and it's supplied by two arteries posterior spinal on the

back side 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 so if it occurred on the stomach side that whole artery which supplies the the 2third of the spinal cord um on the stomach side uh and it involved both sides of the spinal cord it would cause a paralysis of both legs and a partial sensory uh deficit would call loss of pain and temperature because that's where those pathways are

if the problem was on the backs 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 U problems with what's called propri acception 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 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 Venus 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 if the uh spinal cord is involved in the cervical region up high then the arms can be

involved as well 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 yeah that's a good question yes there is uh there there the uh people who who indulge or overindulge uh uh are at risk for developing um uh stroke problem so it's another contribut contributory factor 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 um some of the patients I see uh are not just smokers but indulge in uh other drugs so cocaine mam fetamines uh markedly increase the risk of developing these aneurysms or develop veloping Hemorrhage bursting of a blood vessel and is that because those drugs tend to increase blood pressure during their use um it's because they damage the vessels 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 R 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 metamphetamine can jack the blood pressure up uh and that could cause a hemorrhage in these these um 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 right and throw smoking

in there too it's interesting because for a lot of years there was so much discussion about 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'd drink less or not drink as opposed to drink um but I'm curious what your take is on this well you know this is interesting and um I'm always quite amazed at at um the way people change their behavior based on

one 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 a study showed any wine was beneficial in moderation and um and that used to be two drinks a day for men one drink a day for women and then the latest studies which have been surfacing this year suggest no alcohol is good yeah but you know next year it 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 and here I mean the data across multiple certainly not every study but multiple studies is that um zero to two drinks per week is seems to be the range that everyone agrees is safe at least for non-alcoholic adults um and then once you get out past two 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 four or five servings of alcohol per week it's pretty clear to me it's not a good situation well that was the prevailing Theory until this year and I don't know if you've kept up but in the past you know few months there have been several articles published saying um no wine 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 it counteracts any adverse effect 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 yeah absolutely I I agree with you I'm not heavy-handed about the alcohol thing I always just say you know do as do as you wish but know what you're doing um and I think many people who heard 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 it probably lowers um stress it um probably also disrupts patterns of sleep and they got microbiome so there's you know you you can't escape in biology there's always some uh mod modulatory influence on something else exactly I'd like to take a brief break and acknowledge our sponsor a 1 by now most of you have heard me tell my story about how I've been taking ag1 once or twice a day every

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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 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 whip laap 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 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 hitting the head 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 CU 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 the '90s are good oh they they were super goal contention in fact uh I took care of Steve Young yeah he's a local guy who yeah Steve's a great guy and Steve a really smart guy um uh in fact he has a a a law law 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're recovering from a concussion uh Steve unfortunately had a a a bad concussion at one 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 sequella for football players including uh changes in equipment and and and in in uh tackling and that kind of thing um but concussion is we've learned a lot since the 1990s at that time uh concussion um was not known even repeated concussion to cause CTE chronic traumatic enopi 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 sella and usually there are not long-term sequella um as long as you don't get repeated concussions um so um now what we generally recommend uh if someone has a concussion um we usually get an MR scan if if it's severe Mr scans usually don't show anything 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 the concussion 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 pre-season ey 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 not as well as they they

could on their eye track yeah on their 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 a way you can game the system but uh as long as it's performed well that's a very good way uh of of detecting um subtle problems with the brain well you're a vision scientist so 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 all the

way back to the occipital so it's the whole longitudinal access of the brain that's being tested yeah I'm always struck by when I see these News News Real highlights of you know a player goes down 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 it's per in to me how they would determine that is that you and I both know that the neurons

the nerve cells in the brain 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 a

tricky thing it is tricky and I think we have better uh methods of uh even at the if you're talking about sports on the sideline of doing testing um there are neurosurgeons there now uh who are part of the process um uh 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 periods is not a good idea right just staying home in the dark with sunglasses on also not a good idea exactly so you want to make sure

the brain still has input but you don't want to um overstress it when you recovering from a concussion sounds like doing all the things to keep blood pressure relatively low um LDL cholesterol relatively low so interesting what you said earlier that statins might be vascular protective even in the absence of high cholesterol 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 including conditions like Alzheimer's interesting I know that statens are a bit of a controversial topic um among listeners because some

people um report I think I have this right that statens can give them a kind of a brain fog if they take the wrong one or excessive amounts uh yeah it it I'm not challenging what you're saying I just I just hear the sh the in the comment section and I'm just I don't take a Statin but my cholesterol is in check um but I'm hearing more and more about some of these benefits of statins 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 would want to take an aspirin right because if you have injury 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 what about caffeine is there any evidence that caffeine can increase stroke or resum me I like coffee and I like uh yate 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 relationship unless it unless you're taking so much that your blood pressure is Skyhigh my blood pressure tend lots of benefits uh um evidently to to caffeine in terms of of Health yeah I agree with you there um have a question about something that many people are starting to do now which is to get um exploratory MRI I actually did one of these um I wasn't gifted one I just decided to bite the bullet and pay for it is a whole body scan they put me in the tube did a 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 one white spot on the brain I was told that you could have one 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 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 to neural tissue you know what is your thought on these um exploratory SL preventative 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 and people are getting total body scans so I think there are benefits and risks involved so the benefit 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 tendency to bleed but many times and I see patients all the time who are referred for a tiny aneurysm um blister on a blood vessel in the brain that was found incidentally on a total body scan and these aneurysms which can be one or two millimeters sometimes we don't

even consider those as real aneurysms um they don't need to be treated in most cases 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 iatrogenic injuries that's iatrogenic is caused by the Physicians so uh I think you have to be very thoughtful when 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 um if if if you're concerned but um you know people wonder I have this uh we were discussing it earlier today actually um with one of your colleagues and what if you're found to have a 1.75 millimeter aneurysm if it's really even an aneurysm should you change your lifestyle and for something like that I would recommend no you should forget about it 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 findings maybe we can talk about lifestyle factors because I think anyone listening to this is going to think I don't want a stroke I don't want transient es schic 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 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 uh 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 well I think it has to be individualized to 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 130 130 or under that was considered normal and and would not lead to problems now the guidelin suggests that 120 or lower is better in large you know studies but um as an example uh when my blood pressure gets under 120 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 overing everything I was in my I was Stanford faculty member that over that was a joke

that among Stanford faculty I was 56 and I operated all day in two operating rooms 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 and I emailed on the flight got an hour or two asleep went to the meeting was fine uh it was a stroke meeting with a bunch of scientists uh neurologists and scientists there were about 120 people there were two neurosurgeons there plus me and um drank some coffee at noon

I went for a run cuz I like running and in hu at that day in Houston it was um 90° 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 started to feel lightheaded and um next thing I know I'm looking up at the chandelier and they're they're they're shouting um stroke Cardiac Arrest 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 and after um I'll make the story short after uh a $100,000 workup it was determined I had a faint because I was overdoing it so since then I now I try to get seven to eight hours sleep at night that's clearly the Bedrock of health so I increased I used to get three to five hours sleep at night now I get 7 to nine 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 I'm feeling

a 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 very interesting I've I tend to have low blood pressure it s

of runs in my family to have low blood pressure um I can definitely relate to the um hard driving um ambition phenotype I think it's it's worth people hearing this because it's 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 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 uh 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 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 to exercise less I'm a little bit confused I I also love to run and and do resistance I would recommend they take their blood pressure so um you want to try to correlate any symptoms you're having with vital signs that you modify right so take your blood pressure if you're feeling faint if it's low uh one

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 I can imagine that' be pretty uncomfortable I don't want to be the patient that you're operating on when you have to go use the bathroom 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 hydrate all the time so I hydrate to the point that my

urine is crystal clear all the time and that helps with some of the brain Clarity 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 one of them is they really emphasize hydration they just like hydration water sometimes water with electrolytes if they're working in in in hot conditions just hydration hydration hydration 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 uh and for your kidneys Yeah you mentioned sleep um is there a relationship between sleep deprivation and stroke risk uh that's a great question there's interestingly um Strokes occur more commonly during sleep it's not known why one theory is that it's related to sadian rhythms um I don't know if there's a relationship between sleep deprivation and

and um and stroke I'd like to take a brief break and acknowledge one 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 pottassium are critical for

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l mn.com huberman to claim a free element sample pack with a purchase of any element drink mix again that's drink element.com huberman to claim a free sample pack I'm going to tell a horror story but not I want to repeat not to demonize chiropractors here here's the positive story I had a back thing that my back hurt and I wasn't sure what I needed to do and a chiropractor um gave me some exercises to do that essentially were like the up dog movement in yoga that my understanding is it helped the the disc bulge to

kind of work its way back into the spinal column and it worked terrifically well I took no medic medication I required no surgery and I eventually learned to correct some imbalances that have led me to not have that issue again it was really remarkable and this chiropractor essentially um 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 postto 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 neck adjustment or head adjustment at a car up with a dissection of her artery right and something had happened and she had essentially a stroke yes 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 uh um an alarm and I decided at that point I would never allow a chiropractor to adjust my neck 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 either the uh vertebral artery in the back or the cored artery up closer um in the front so no cutting when you say dissection they're Mak basically making an adjustment

yeah well what happens is um and I agree with I 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 um the manipulation of moving the bone and the soft tissues causes a tear in the wall of the artery and and what occurs interestingly is that the blood that's usually in the space the Lumen the middle of the artery gets into the wall and

causes a false Lumen a false passage and that that blood in the wall pushes part of the wall into the the main artery obstructing flow and sometimes causing a clot to form that can be dislodged and go up to the brain yikes so 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 um 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 exercis is 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 one 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 no evidence that it's bad oh good oh good maybe I'll get an inversion table again um as long as you don't stay there of course you had some okay great um would you 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 rug like any sport uh it's a team sport a lot of good skills are learned um 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 is 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 R for injuries not just head injuries other injuries um my son who's a very good athlete he played four years of High School uh baseball and soccer was asked to

try out uh for the quarterback position his senior year 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 gun high school he went to meno okay I went to gun our football team was at that time was bad enough that there was no incen to play what about soccer and heading the ball I've 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 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 a 49ers uh neurosurgeon back in the 90s there was very little data although there was some evidence even then that soccer players had a uh High incidence uh particularly female soccer players had a high incidence of of concussion surprisingly uh 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 I feel like if a sport is not your profession 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 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 one point about you know continuing to play or you know finally deciding 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 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 maybe 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 um maybe we can Circle back a little bit on a a fairly common scenario um 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 recently our 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 does one need to worry about one kind of dizzy inducing head hit um 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 I don't think you need to worry in general especially if your symptoms resolve within a relatively short period of time such as how long a day or two yeah I mean you know even if you have a mild concussion and you recover within a day or two I don't think there's uh any need to worry or get a scan or uh and and it's a common place Place occurrence yeah I think um your answer will set a lot of Minds at ease because um

people do worry I mean 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 it's just you know it's so hard to know what's going on in there well as you say that's why we develop very thick skulls to protect the the most important organ because after all the tissue doesn't regenerate um at least not much of it there are a few areas where there where there neurons that can replenish you know I'm going to take um 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 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 stroke traumatic brain injury spinal cord injury uh uh and um other diseases uh ALS lugar's disease um Parkinson's disease now we are learning learning that uh there is hope 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 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 but um for instance we've done studies and this is still in um clinical trial phase with patients who are years out from a stroke they've been through rehab uh they've been through physical therapy and 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 and now we are finding in some

of our 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 and stimulate coupled with physical therapy intensive Physical Therapy you can improve arm function in those patients in our patients that we've treated in multiple trials we're seeing early indications that patients years out from a stroke can start to recover function in their arms in their legs in their

speech 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 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 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 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 resent 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 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 disrupt 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 gone done a lot of physical rehab um obviously a really hard situation but it told me that often times when we think that All Is Lost not All Is Lost even in people in their 70s right

it it has to do with plasticity 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 one side usually they can make an excellent if not complete recovery um this is the as I recall from my undergraduate years the Kenard principle if you're going to have a brain injury have it early in life exactly 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 six years old cuts herself the next day it's totally healed so little kids are like salamanders right they almost it's 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 kids can regenerate without a scar they can often

times they can't grow an entire hand back but it's kind of striking how much plasticity 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 as an example can prom remote plasticity in a sense we think what's happening is um that these methods 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 so they were meenal or uh another group made the cells from uh from fetal uh neural tissue okay so just to orient people inside 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 hemopoetic population so a population of of sort of 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 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 become neural cells neurons that will incorporate into the circuitry actually that was the initial notion 20 years ago when we started doing this was that these cells you put in uh become these exogenous

cells you inject become neurons and asites and alod dendrites all the cells in the brain and that the neurons reconstitute circuits that is not how they work the way they work and this is why it may not uh matter what particular type of stem cell you put in the way they work primarily is by secreting very powerful proteins molecules growth factors that promote native recovery so they promote 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 so by modulating somehow the

immune system in the brain they are able to induce plasticity and recover function interesting I I'm tempted here to weave in the the stories that date back to the90s 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 Dage Gus of the hippocampus the olda factory Bulb Etc that upon hyper oxygenation 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 DM 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 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 improving in some cases but the other side of the brain is showing increased activity 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 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 Scher and um

Teresa Jones I yeah I know you familiar with this yeah we almost recruited to to to our department 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 one side of the brain uh because of the way the circuits are organized and of course you know this better than anyone uh Gary but that one 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 to um sort of uh tie up the 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 one that should deserve more attention yeah it's called constraint therapy and um not only has it been shown in uh animal studies preclinically but it's been shown in some uh clinical studies of patients with stroke in fact one of the trials we did with transplanting stem cells into the brain included restraining the good limb to force

use of the other limb so there's um some very intriguing data suggesting that that's important however some of the 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 an important temporal Factor there in terms of the timing of when you do that is there anything that people can do or take for neuroprotection after an injury to essentially try and rescue neurons that would otherwise die 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 different pharmacologic agents were tried um probably um a thousand different drugs were tried which blocked 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 and it takes some time and it's actually an active process so the release of these excitatory amino acids occurs so normally as you know glutamate aspartate 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 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 and then there are other Pathways that can that lead to release of free radical and uh which are more damaging and those can cause another type of cell death called apoptotic cell death that's

a cell death that occurs and requires protein synthesis 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 um within a few hours but it never

was able to be translated to the clinical Arena except for one case so besides drugs that were tried um another method of protecting the brain was tried called mild hypothermia and that uh was a process of reducing the brain temperature and body temperature just a few degrees from 37° centigrade to 33 and we were one of the first to to show um that that was protective even after the stroke in animals um my understanding is that when you cool neural tissue you quiet its electrical activity in fact this is a common um tool for experimentation

in in Neuroscience Laboratories you know you want to shut down a a brain area transiently you you cool it down 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 uh and make a complete recovery because their body temperature is dropped down to very low like 20° 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 partly the release of those exitor amino acids glutamate it blocks the calcium influx it blocks the inflammation uh and so um that's probably why it works so well it even blocks that other pathway of program 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 prospec of randomized studies that one type of

stroke actually two types I should say two types of stroke are benefited by cooling the brain quickly one is cardiac arrest from ventricular fibrillation and prospective studies which were published in 2002 showed that if you uh cool patients who have cardiac arrest and then are resuscitated out in the field down to between 32 and 34 degrees Centigrade from 37 much better outcomes neurologically that's from Global eskema 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 hypo schic injury

those are neonates who have lack of blood flow for some reason to 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 they have better cognitive outcomes so for cardiac arrest in in uh in the mid 2000s uh I think it was 2003 the American Heart Association determined if 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 you know Mouse and and rat Stroke by Cooling I started cooling my patience in the operating room um because I I felt you know even if it hasn't impr proven in in in patience 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 so back in um the 1990s I started cooling all of my patients we started by cooling them by putting um packing them in I and putting alcohol on them but uh the operating room staff appropriately didn't like that cuz cuz alcohol is inflammable so then we started using cooling blankets 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 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 cooled 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 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 it hasn't been proven yet for the kind of stroke we've been talking about where there's a single blocked 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° 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

soles of the feet the palms of the hands and 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 that obviously have clinical applications but but also you would imagine for some of the things we were talking about before like just to um provide a bit of neuroprotection after a head hit or provide a bit of neuroprotection perhaps even as it relates to aging you know spending a little bit of time maybe 10 minutes a day you know not badly

hypothermic please people but slightly hypothermic and then bringing the body temperature back 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 snow bank 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 it's called mild hypothermia because it's just a few degrees 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 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 inter fear with um other um metabolic functions and clotting parameters and there 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 cooled them we think it it it made a benefit for instance we had one 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 so we um uh and and it lasted 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° before we by the time it had happened and um and then we finally uh got the heart started we ended up putting some uh restoring flow through catheters and and a heart lung machine and remarkably the guy 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 uh we certainly know it it's true for cardiac arrest and Global esia what are your thoughts on Plat

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 um spin down platelets and then put in platelet rich plasma um a few years ago people were making claims out there about PRP containing stem cells I 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 starting 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 what's whatever 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 one has to be

a little careful for instance um I still um get um emails uh you know every few weeks from people saying uh I've had a stroke or I've had a head injur 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 another podcast I have not I I'll do a solo episode on stem cells and what they are and what they aren't I I just will just sorry to 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 I was going to bring that up to and that's what led the FDA to really clamp down on stem cell clinics in the US although they haven't clamped in on those type clinics as well they should but I um I tell patients no 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 you

don't know whether these sell where they come from sometimes they're not published literature um you don't know um where they're derived we've seen cas es of patients going elsewhere getting injections into the brain or the spinal cord and developing tumors or other problems so I discouraged 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 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 meenal stem cells and it was reinjected into the into the eye should have been safe right 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 a first inhuman trial at Stanford using 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 one study and we we're making uh plans to do a phase two study with control patients which you always want to do uh but despite the Hope 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 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 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 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

b 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 intraarterial threading a cath up as we discuss and injecting in the brain those cells it turns out don't even get into the brain um and the idea is that uh in some of the better studies that that have been done in animals that they work by modulating the IM immune system systemically those cells get trapped in the lung in the spleen which people describe as bioreactors

and modulate the immune system which does make some sense as I say we we think one of the main benefits of these stem cells is that they modulate the immune system uh and that helps with plasticity in the brain but even intravenous delivery can be can be dangerous to the brain yeah this is an area that uh we will spend a lot more time on during this podcast um 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 that uh features those data or that uh is where those data arve from rather um are really impressive I mean some people who were largely IM mobile 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 the future of stem cells in stroke therapy um is pretty pretty bright at least from where I said yeah we don't want to oversell this um but uh some of the uh results in certain patients are remarkable I mean the patients and their

families has 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 17 of the 18 U uh intended patients uh 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 phase three 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 46 million in Grants and philanthropy um getting it to this stage wow yeah wow that's that's a lot of time and a lot of money amazing that's way science and and and translation to clinical medicine is um I would be remissed if I didn't 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 in medicine I mean for instance if there was um five times as much money um would the science progress at you know five times the rate probably not um no but M money is a factor um it's not the only Factor uh the FDA is 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 um 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 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 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 yeah 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 going to have to because for the next trial this trial I was for forunate to get a grant from surm California Institute for regenerative Medicine of $12 million

that's taxpayer dollars exactly great use of taxpayer money putting into really Forward Thinking research 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 about 69 patients that will cost at least 45 million um and as the trials get larger even more so uh yeah we need to figure out a better way to allocate money

to to make these advances it sounds like um a company or some role of industry is going to be necessary a um well you might be interested in investing right I mean well that the um the this podcast is always available free the standard La podcast our premium channel um actually generates uh money we do uh askme any 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 sulk Institute Columbia University we've already done that we're going to do more of

this well I was I was big fous oh no listen we could explore it one of the one of the guidelines is that we fund research on humans exclusively um so we could talk about that the um a 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 two kinds of Stanford faculty Stanford faculty with companies and Stanford faculty with successful companies so um we'll we'll see if 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 these little companies like you know Chente and you know other companies like that that um are not strictly Stanford relations but of course other universities too but you know the universities are where the basic research is done and then then somebody has to implement 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 shway and radiation oncology uh Henry Kaplan who had developed the first radiation uh method for treating lymphoma uh and we were great at making basic discoveries is not very good at translating them but over you know the last what 50 years Stanford has gotten much better at uh translating them um uh into you know clinical therapies uh and even doing some of that work at Stanford 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 to um big Tech um 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 the most rapid possible flow between basic science Discovery and um implementation at at large um I want to make sure that we cover just a little bit about vagal stimulation a lot of listeners this podcast are familiar with the Vegas nerve

as this very extensive pathway connecting brain and body in both directions um the common idea out there is that the Vegas is associated with calming because it's in the parasympathetic arm of 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 can be about alerting the brain um or making the brain more alert um so what

sorts of vagal stimulation are you doing um given that the vagel pathway is so um extensive you know like like which branch of the Vegas do you stimulate there's it goes around the ear it's in the neck it goes down through the gut I mean we're talking basically about a super highway of I mean it kind of reminds me of the Austin freeway system if you've ever driven in Austin it's like the freeways go in every which direction that's so whenever I'm there I'm like the freeway system here is kind of like the Vegas so

which um Avenue 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 and it was shown in the study that compared with um non-stimulation in other words putting the stimulator on 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 three months now recently at the last International stroke meeting last uh this past February uh it was presented and I don't I don't know if it's been published yet that those results hold up for for a uh up to a year so um the way it works presumably is that you stimulate the entire vus nerve in the neck and it's not the peripheral effects on the heart or the other autonomic organs where it's working it's stimulation that goes back to the brain right because when you stimulate a

nerve it doesn't go in One Direction and that's probably how it works for depression also not a systemic but and the Vagas has lots of connection with brain functions right um and so that's it's not completely clear which areas are being stimulated to recover from stroke or or improve depression but it's brain stimulation that somehow again resurrect circuits or induces plasticity in circuits uh again it's it's 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 diseases and injuries is the vagal stimulation uh is it invasive or can you use an external stimulator it's invasive you have to do an operation it's lowrisk um very few side effects occasionally there are some it can cause some problems with swallowing which are usually temporary right because the vagal nerve um the recurrent vagal nerve supplies the the laryn the vocal cord but um so it's an implanted stimulator but the stimulation could be turned on and off with an external um magnet device incredible 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 patients I know you're still in the operating room you were our department chair for more than two decades 25 years 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 nicotine fortunately caffeine's not on the list but don't overdo it folks um neuroprotection the discussion about TBI something we've never discussed on this podcast um transient esumic attacks and just a really vast survey of things that concern a lot of people and that also now having uh heard what you've shared also 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 Andor enjoying this podcast please subscribe to our YouTube channel that's a terrific zeroc 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 five-star review please also check out the

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