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

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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

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huberman speaking of Lifestyle factors

um anytime we hear about traumatic brain

injury or concussion people immediately

seem to think about football um but I'm

told by colleagues of ours in

neurosurgery at Stanford and in

neuroengineering 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

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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