Concussions — Mild Traumatic Brain Injury (TBI)

[APPLAUSE] >> Wonderful, so now on to tonight's program As many of you may know, I am big, but I am not Big H, also known as Harold Lavender, which I'm sure many of you know

Harold, unfortunately, could not join us tonight, he is in Los Angeles visiting his children, but he wanted to pass on a message tonight He said Dave Hovda and he worked together at the Arroyo Rosa, Deloso golf course in the early 1970s Apparently Dr Hovda caddied for him in several tournaments And the skill in his difficult job clearly helped define his future academic successes

>> [LAUGH] >> The caddie fee of $1 was put into your college fund, so he appreciates you for all the help there He welcomes you back to the University of New Mexico and wishes the best for you >> Thank you very much >> Just to go into a couple points here So Dr

David Hovda is a proud three time alumnist of the University of New Mexico He is the director of the UCLA Brain Injury Research Center and is a past president of the National Neurotrauma and International Neurotrauma Societies In 2016, Dr Hovda received a lifetime achievement award from the National Neurotrama Society Additionally, Dr

David Hovda Research Award was established to recognize the highest rated high school undergraduate post baccalaureate poster presentation during the annual National Neurotrauma Symposium He has consulted with Major League Baseball, the National Baseball League, National Hockey League, and the World Boxing Council In 2012, Dr Hovda received the Alumni Association's James F Zimmerman Award, one of our highest awards as the Alumni Association So if you would, please put your hands together for Dr

David Hovda >> [APPLAUSE] >> Thank you, thank you very much So Big H couldn't come tonight? >> [LAUGH] >> So is everybody here a Lobo, woof, woof, woof? [APPLAUSE] >> Either that or you get an eight count from UCLA [LAUGH] >> So I did caddy for Harold Lavender a couple of times And I remember this par three

It used to be called the south course, now it's called the championship golf course And he turns to me, it's a par long par three And I know he's gonna watch this later He turns to me and he says, Dave, he says, what club should I use to hit? [LAUGH] It's par 3 And I said laddie, I've seen your golf swing all day

You haven't got a club in the bag that'll make it >> [LAUGH] >> A little bit later in the presentation, you'll see Harold Lavender's golf swing And I'll point it out to you, since this is about brain and brain injury >> [LAUGH] >> It kind of goes together So seriously, one of the things that I have got to say is how grateful I am to Kim Feldman for inviting me to come to speak And to come home, to come back to my roots

The University of New Mexico has done so much for my career And I got such a wonderful education I wish more people [COUGH] had the opportunity I had by coming to this wonderful institution When I left here I went to UCLA in 1985, actually 1984 to 1985, it was kind of a crossover, with the idea of just staying there for a year or so and then moving on Cuz I didn't think I was going to be smart enough to stay there

I'm still at UCLA, and I'm gonna be retiring from UCLA [LAUGH] And so I've done something that I guess is okay as far as UCLA is concerned The brain and research center was started in 1990 It was recognized as a state of excellence, center of excellence, by the National Institutes of Health for traumatic brain injury and recovery function So I'm gonna divide this lecture up into some very similar, very simple parts

First part's gonna be what a traumatic brain injury is You will all know how to beat somebody on the head, all right? My job is to tell you what happens inside the head when you beat somebody And then the second is I'm gonna tell you a little bit about the basic science of what happens to the cells inside the brain, very small, very short No formulas, I promise, no exams, nothing like that There may be one diagram that's a little crazy, but it's important for you to see

And then we're gonna talk about a little bit about, what concussion is and why a concussion should be considered much like a traumatic brain injury And at the end, I can talk to you about the long term effects of mild traumatic brain injury or repeat concussive blows And we can talk about the definition of sub-concussive injury and whether that really exists or not And then I'm happy to answer any questions you have about the National Football League, about playing soccer, about heading the ball being in soccer, about athletics About whether, if you had a son would you have your son playing football? To get it off the table, I played football

I was never good enough to play for UNM, but I did play football I was a middle linebacker I was never taught to put somebody gently down on the ground, on a I was told to kill somebody as they came across the line of scrimmage So with that said, you're gonna see both animal works and basics science work and some clinical work

And then we're gonna combine it all together at the end And we're gonna make some general statements about mild traumatic brain injury and what it's about, and how we should approach it, both from a sports standpoint, as well as from a healthcare standpoint First, disclosures I'm a tenured professor I don't have any stock

I don't care about the National Football League I've never been charged with sexual harassment >> [LAUGH] >> I don't do anything fun! I don't do anything weird I'm just a professor, okay? I don't care if they kill each other on the football field, or on the soccer field, or anything like that One thing for the students, for those of you that are students or young professors in the audience, I think it's really, really, really important that you acknowledge the shoulders that you stand on

And this person up here at the very top is still alive His name is Dennis Feeney He was a professor here In psychology He introduced me and a guy by the name of Gordon Hodge to physiological psychology And from that moment on, I fell in love with the brain

And I didn't know how I could ever study anything else except the brain This person here was the chairman at Johns Hopkins for neurosurgery His name's Earl Walker, he retired and came to New Mexico and because a professor emeritus And he and I did studies together on the definition of cerebral death And I'm happy to talk to you about that, but that's a different lecture All right, I went and did my post op with this man here

He's a neurologist, his name is Jaime Villablanca, and there I learned cerebral hemispherectomy That's the removal of half of the brain for children that are just born that have infantile epilepsy or Rasmussen's disease And you can remove half of their brain, and you know what? They go to high school, they go to college, they become doctors, they become administrators, they become lawyers But if you do the surgery too late, there's not enough plasticity left I've got a whole set of lectures for that too, but we don't have time to talk about that

This person here, Donald Becker, he came to UCLA the same time I did, and his specialty of interest was traumatic brain injury And I went to the emergency room and I saw my first traumatic brain injured patient there And I realized that they needed something completely different than what we were able to do in a laboratory as a basic scientist And it was frustrating to me in the 1990s that we had nothing to offer anybody that had traumatic brain injury There was no treatment for recovery of function

Rehabilitation, physical therapy, and occupational therapy help, they improve the quality of life But there's no drug that I can give you, there's no experimental neurogenesis of cells that I can give you to repair the brain So what is traumatic brain injury, well, it's really caused by a mechanical force, a biomechanical force I can't tell you the number of times people have come to me and said, well, I've had a head injury cuz I've had I've had a stroke or I've had a seizure or something like that Traumatic brain injury is like a baseball bat, you get hit by a baseball bat, or it's an assault

It's biomechanical by its nature, it's not a stroke or it's not ischemia It can produce cell death, but in many cases, it produces a regional and temporal cellular alteration of function, it produces a state of energy crisis Energy crisis, how much energy does it take to run the brain? I'll teach you, I'll tell you, this is really cool, and a subsequent thing called metabolic diaschisis, well, what the heck is diaschisis? Well, that's a fun term that was used by, a long time ago, it's mostly used today by neurologists But it usually means, it literally means shocked throughout And it means that something's going to recover eventually, it shows deficits and it will recover, and I'll teach you what that means

It changes the priorities of fuel, the brain, all of a sudden, doesn't use the same fuels that you thought it used normally, after brain injury And it causes the acquisition of post traumatic stress disorder, or neurological degeneration that's related to different diseases All kinds of diseases, not just chronic traumatic encephalopathy, which you've all heard about This is a guy by the name of Lee Goldstein, He's a friend of mine from the University of Boston He sent me this from New York, And this is a papyrus from an Egyptian physician

I'm sorry, I can't interpret it for you, I have to take their word for it But it just simply says, it's really important to understand if somebody gets hit in the head, cuz they're different after they get it in the head, that's what it means, okay So we've known that this is a problem for a couple thousand years, okay Constantin von Monakow worked with a guy by the name of Broca, or not with him, but at the same time And Broca was the man who discovered that language was located in the left hemisphere

Well, van Monakow would have people that had strokes in the right hemisphere And they couldn't talk for awhile, and then all of a sudden, they could talk again And so he wanted to coin a term that was temporary, that caused a temporary dysfunction that you slowly recover from And he called that term diaschisis, and he did this in the early 1900s Earl Walker in 1944 wrote what I think is the seminal paper about concussion as a mild traumatic brain injury

And when I gave the talk for the National Football League in Hamilton, Canada, I learned a phrase that I thought was very cool Now was l, l don't know what is so mild about mild traumatic brain injury, l just don't So let's talk about energy, l told you energy's important, all right, so you run at about 522 amps per second All right, you make about 65 kilograms of ATP a day, that's energy, that's a type of energy, adenosine triphosphate You consume about 380 liters of oxygen per day

The average human burns at about 116 watts of power per hour That's kind of like a dim light bulb >> [LAUGH] >> Now, there's this junior college in Las Cruces >> [APPLAUSE] >> [LAUGH] Having gone to Washington, DCseveral times, I can tell you, there are some pretty dim light bulbs that I've seen

>> [LAUGH] >> So what happens when the brain moves? People take a model of a human brain, they'll say, yeah, this is a human brain This is about 360 grams, you can play football with it, tuck it under the arm, that kind of stuff, it's always rubber And even in the gross anatomy lab, when I would take the brains out of the skull, they would be fixed, and they would be hard and they would have them in the jar The students would pick them up and hold them, and they'd play with them But if I take you to the autopsy room and I take a brain out of a human

Just from autopsy, without fixing it, it's like undone Jell-O It'll almost go flat, it's like undone Jell-O And when it's moved violently, it's not moved in one, like this and back It is moved the same way that this finite element looks like where you have different parts moving at different degrees And that's because different parts of the brain have different consistency

When you start putting your finger through the human brain, you'll have different parts of resistance, and that's simply because some of it's thicker than others Okay, and it consequently will move differentially than others And when it moves differentially, that causes distresses, and strains that pull a brain apart, and pull the cells apart So how do you do this in an animal model? Well, it seems kinda ridiculous to take an animal, take a hammer, bang it over the head, and that sounds real scientific, doesn't it? Doesn't sound very humane, so many, many years ago in Sweden, they discovered there's a certain way to do this This is actually discovered, actually Wayne State University, by a bioengineer

What you could do is you could take a small squirt gun, this is a cylinder that's filled with saline And this is a hammer that you can drop down, hits a piston, generates a fluid pulse And then it generates and you do a little hole in the rat skull and it pushes a little bit of saline into the skull and it moves the skull and moves the brain at a certain distance and a certain velocity So, those of you that remember physics that's called work, which is force over distance but now we're gonna divide it by time All right? Now when I was here, I asked a lot of girls out for dates I did man

I worked it hard, I was a member of Lambda Chi Alpha and I worked up and down the street I asked them out And every single girl would come to me and they would say no No, no, man, no No, no, no, no

I didn't give them a concussion But if I had Mike Tyson move their head that same distance over 21 milliseconds, they'd be out like a light So it's not necessarily the movement It's the degree of work that the brain actually receives Well, if you drop that hammer at different degrees what happens? Well, if you make the concussion very very mild and then you increase it and you measure what happens inside the brain

What happens inside the brain is the brain releases a chemical or an ion called potassium and Laou discovered this in the 1940s And it causes a depolarization It's very very brief It only happens if you look at this slide here, it shows the increase in potassium that goes up like, it will last for a couple of minutes here After the traumatic brain injury

But you'll notice that compared to [INAUDIBLE] you have to get to a certain part of severity, then all over sudden it happens And then you get this release of potassium And we thought my goodness if you have this release of potassium mother nature doesn't like that, and she would like to have that potassium go back into the cells so that cells can fire again Because if the potassium stays out of the cells, outside the cells, the cells can't fire And become depolarized

That's called spreading depression So we thought well, maybe the brain requires energy to activate these pumps So, Louis Sokoloff in 1977 discovered how to do this And this is a slide of a rat brain Here's the arrow showing the fluid pulse, and the red is in the increase in glucose use

And the glucose is burnt And so we have called it the burning of glucose to concussion or traumatic brain injury And it burns at 200 times the amount that the normal brain would work It's an enormous amount of glucose that's burned And glucose is a fancy term for sugar, is the primary fuel for the human brain

Now we thought, well gee, I wonder why we did this, what happens? Well when we do this in the animal literature, if you look at this hippocampus here, you can see that it's burning really hot It's really hot with glucose utilization But if I cut the fibers, which are the glutamatergic fibers, the brain, the hippocampus, isn't black It actually is quiet And actually, if you measure, what happens, you actually see the increase in lactate

Well if you remember, if glucose is burned, and you don't use oxygen, or you don't have enough oxygen You make something called lactate And you make something called lactic acid Have you ever tried running up the stairs like at the pit? We used to have seats, we were kids And the student section used to have seats

Now they don't Which I find odd [COUGH] but anyway >> [LAUGH] >> If you run up those stairs the first thing that starts to happen is your thighs begin to burn And you wonder why that happens, well it's called lactic acid and so lactate will be formed in the brain Lactate also is a signal in the brain

It's an important signal and I'll tell you what happens So, in cartoon fashion, let's see what we do here So let's take our hammer We hit this neuron, okay? All the cells in the brain fire It's like having a mini seizure

And the cells release glutamate and fire, and the glutamate binds onto a receptor, and potassium is released outside the cell And Mother Nature goes [LAUGH] This isn't good We gotta get the potassium back in We're not killing the cells

We're just making them dysfunctional So what happens is we have this pump called the sodium potassium pump and Mother Nature says, okay, well, we'll take this glucose We'll make some ATP, we'll drive this pump and we'll pump the potassium back in and everything will work just fine And this is the first part of the energy crisis that occurs following a concussion, is that the brain needs to burn It needs this glucose

So we began to say, what happens over time? What if we do this and we study these animals over time? So when we do that we find that in fact, if we do it at time zero we give the animal a concussion You see this red area burning Then at about one day the brain becomes depressed And it's like it's exhausted It's burnt so much

It's exhausted So it stops and it rests Mother Nature has a chemical that's released, it's called adenosine It senses, I want to rest And then it will slowly start to increase and it will recover back to normal

And while it's dysfunctional, during this time the animals will show cognitive and spatial deficits as well as motor deficits But you know something? It's not how hard you hit the brain This happens whether you hit it severely, or you hit it mildly It's the time that you spend in these states that's related to how severe the injury is in the animal Well potassium is not the only ion that we're worried about and [INAUDIBLE] we've known for years that calcium if that comes into the cell you can kill the cell

Calcium is hundreds of times higher in terms of concentration outside the cell than inside the cell So if you open it up a little bit the membrane it comes rushing in and calcium will come rushing in what happens is calcium will rush in for four days So you have potassium which releases for about two or three minutes, and calcium which goes in for about four days This happens there is no cell death yet, we are still not talking about cell death We are just talking about a dysfunctional neuron or dysfunctional cell

And we are talking about a vulnerable cell So now, we have this cartoon again Where we have calcium coming in, and the neuron melanocytes says you know something? I don't like this calcium, this calcium's gonna kill me So you know what she does? She's really smart She says i'm gonna take the mitochondria and it's gonna capture the calcium

I'm gonna buffer the calcium So it's gonna go to the mitochondria and all of a sudden you can't make the ATP You can't make the glucose So now you need the energy Calcium comes in, shuts the ability of the energy to be made

And that is your, if it gets bad can cause and cell death And that actually causes more dysfunction In the axons this can happen as well Calcium can come into the axons And you can have axonal swelling and inflammation

And this is the way cells communicate to one another through the axons And this can actually cause microtubular damage and neurofilament damage and plugs And so what happens is that you have a neuron now, that is vulnerable because it's very weak Because it's trying to recover from this blow that you gave it And it's also can't talk to its neighbor, that's why people have deficits, that's why you have amnesia, that's why you have unconsciousness

That's why you have things that are problem following a mild traumatic brain injury Well, that's not just the only bad thing that happens If you take a normal animal and you stimulate the cortex you can have an increase in glucose metabolism and you have a corresponding increase in cerebral blood flow The brain doesn't store glucose It doesn't store it

It gets it from the blood That's why magnetic resonance imaging works so well for functional magnetic resonance imaging Yeah So, what happens is, when a cell fires, it asks for more blood And then the blood is coupled to the energy demands of the tissue

In this particular case in the normal case there is no cell death This is the way we all work We work on this everyday This is when we read, we look at lights, we listen to a lecture We go to sleep when somebody is lecturing

You know whatever happens But after a concussion, up to three days after a concussion I can stimulate the brain I can still get in increase in glucose But i don't get an increase in blood flow And now the cells die, so they die

So I have a vulnerable brain, if I stimulate it while it's vulnerable, it can't make the energy that it needs It can't survive the signaling Because the signaling pathways are gone And now you are starving it to death Because the blood flow doesn't get to the part that it needs

If you plot all this out, this is an enormous amount of science, and it's not just us It's across the world This happens to be a neurochemical, metabolic cascade, and this isn't a rodent and a rat And this is in minutes, hours, and days, and these things, calcium, potassium, lactate, blood flow, glucose, all these things happen in different time courses So it's not that it happens all at one time at the same time

That's why one chemical, one bullet, there's no silver bullet for traumatic brain injury, it's gonna take a multiple compound, where it's gonna take multiple treatments And this is what we've termed the cerebral metabolic crisis When calcium comes in, calcium will bring in sodium into the cell So those of you that had breakfast or lunch today, and you I'm married to a cardiologist, so I'm doomed But you go and you put a little too much salt in a french fries, and you eat the french fries, and your fingers begin to swell

Same things happen to the cell, when the cell gets sodium inside of it, it swells and that's called edema That makes a tight brain So now, inside the skull, the skull is a closed box This is a closed box, this is your helmet [SOUND] It's closed

If I open it, and you come to my house, I serve you peanuts on this >> [LAUGH] >> This side On this part, it's got ridges in it, okay? But the point is, that it's got a closed box except for this hole, this is where the brain stemcomes out If the brain swells, and it's closed, what happens, it will swell, try to come out the frame in and it will crush your called herniation it can crush the brainstem and it can cause death And so this hole here, which I just showed you, is the exit for edema

So you lose a few neurons, what's the big deal? When I started medical school here, graduate school I was told you are born with so many cells You have a martini, knock off a couple You got a million of them, what's a few cells that are gone Well, let me show what happens

I'm gonna show you Harold Lavender's golf swing >> [LAUGH] >> You're gonna see a line of guys in a driving range, and gals, on a driving range, and you're hitting golf balls Think of it as a neuronal network, a network of cells that has a function Okay, and then we're gonna bring in a neuron, another person, and I'm gonna show you what happens See if this'll work

>> So here's the network So these people are hitting golf balls Harold is the third one from the left >> [LAUGH] >> And along comes a real important neuron >> [LAUGH] >> And the neuron next to him sees this guy, and he goes, God, did you see that? That must be wonderful

So he tees it up, and he says, you know something? I'm gonna hit it the same thing he does So he hits it Harold's frustrated Harold sees this So Harold says, well heck, I'm gonna swing same way

So he swings the same >> [LAUGH] >> So this goes on and on and on, all the way down the line until they're all swinging And they're all making beautiful music And then all of a sudden we have a concussion and this neuron becomes dysfunctional and leaves You know what happens? >> [LAUGH] >> It's cute isn't it? [LAUGH] When is it time to return to play and when do, when does, what happens in repeat concussions? Well concussion, football is getting a lot of press

But concussions happen in boxing, they happen in cheerleading, they happen in lacrosse, they happen in field hockey all kinds of different sports There are 44 million annually children and adolescents in sports in the United States 62 million of them are high school athletes 340,000 are college athletes who are going to get transgressions and 144,000 are pediatric concussions that go to the emergency room, okay? There are 2 million Americans that are going to get a head injury this year, 2 million So what we did is, Miami Prends, who is my graduate student, began to look at this metabolic cascade And here's the glucose spike, and it slowly begins to recover

Here comes another one that came along Well, we've only give it injury during the time that it was our cell's beginning to recover it now takes longer to recover from an injury and cells die So we became very worried that repeat traumatic brain injury can cause other types of problems besides just long term problems and injury So we saw now repeat injuries We saw cell death along the ventricles in the animals

We saw a change in the decrease in body weight, and delayed puberty in very young animals We saw a decrease in growth hormone Today you now when you have a head injury and are recovering from a head injury, you now are tested for hormones Primary growth hormone, as well as testosterone Excess testosterone is also decreased for a long period time

And sexual behavior, your libido changes after traumatic brain injury for 16,17 year old, that's a big deal Now, I have not met any rat that's a human I have met several humans [COUGH]- >> [LAUGH] >> Are you listening, Harold? Or it's a rat? This is Mr Gonzalez and Mr Vespa, Dr

Vespa runs an intensive care unit And this is our PT scanner And this is how a PT scanner works What you do is you take an atom and you add a proton to it It wants to get rid of that proton, it runs into an electron

When it hits the electron and there's neighbor in it, it gives away 511k gamma ray and it's detected So we can tell what happens So we can measure glucose or oxygen or blood flow in human patients without killing them, without doing the same thing doing the animals So for this experiment, I'm going to show you this is just a color bar just for your reference section So the lime green is about 7

5, all right This is a girl that came in, I'll never forget her name, name was Chapman and I have her permission, her family's permission to show these slides She was an 18 year old female in a motor vehicle accident She was hypoxic at the scene She was a Glasgow coma scale of 4, she was very close to cell death, very close to death

And we did a PT scan on her Look at a burn Look at the red area on the top part of the slide, that's burning She lived for nine years in a vegetative state before she died And when we did this over this time course of patients, we saw the same thing we did in the rats

We saw an increase in glucose metabolism, a depression and a recovery, the function overtime Again, we were concerned about whether it was a degree of severity If I look at these images, these are glucose images This is cerebral blood flow This is oxygen

This is oxygen extraction fraction This is all one patient It's not the color It's the intensity that's important They should be matched

The same parts that are really bright red here Should be really bright red or white here Should be really bright green or red or white here, and they're not We've lost the stoichiometric relationship between glucose metabolism and oxidative metabolism in human beings the same way we do in animals This oxygen extraction fraction is the amount of oxygen that's taken from a unit of blood as it goes through the brain

This is not cerebral ischemia This is traumatic brain injury And then this happened This scared me to death So I had the coach, I'm sorry, the athletic trainer for our football team

Our football team practices on campus, doesn't practice at the Rose Bowl And Jerry Fireman who is the physician called me and says David, I've got this kid that had a concussion would you like to image him? And I said yeah, I would love to image him So, I happened to have at the same time a woman, a person that came into the emergency room with a severe traumatic brain injury, and I had a slot open the next day So I went to the practice field, and I got this guy, and I talked to them I tried to remember everything that I learned in the Department of Psychology here at UNM

Who's the president of the United States? Who is your girlfriend? What classes were you taking? What do you wanna do? And he said, I don't care what you do, Doc I'm happy to help you with your research, but don't show this to the combine cuz I wanna play professional football So I went out and I found a [COUGH] normal UCLA undergraduate student That's kind of an oxymoron >> [LAUGH] >> And I ran a PT scan on him

There's his PT, that's what a normal [INAUDIBLE] looks like So I did the two people, one who had a concussion the other one that had these severe traumatic brain injury same age And I called the technician that night and I said show me the concussion patient She said that's the concussion patient I said no, that can't be the concussion patient

Show me the severe injured patient She said that's the severe injured patient It doesn't make any difference for your Glasgow coma scale of 15, which is normal, or a 5, which is severely injured This is a biomarker for mild traumatic brain injury This is a way of looking at a picture of concussion Where one thing is very obvious that happens to people that have concussion in the football field, any athletic trainer will tell you this, any doctor will tell you this, athletes lie

Are you okay? I'm ready I'm ready to go back at it Same with military personnel In Europe, Vagnozzi did the same work only he did it in people who played soccer and rugby And he looked at patients with [INAUDIBLE] spectroscopy and he looked at NAA to choline ratio, which is a measure of mitochondrial functioning

And notice that in the frontal lobes of a single concussion they took them about 30 days to recover So they did the right thing They took these players out of play, told them they couldn't play for a while A couple of them sneaked back out and played, got hit again So they did the same study

Looked at it and now it takes 45 days for them to recover Just like in the animals So when you look at a head injury that has a right contusion, and you look at a spectroscopy that shows a lot of lactate And you have a microdialysis probe here, you can see there's no glucose but lots of lactate The brain has burned every single mole glucose it has, there's [INAUDIBLE]

The same thing as burning your thighs as you're going yup and down the stairs If l put it in, look at different reign of the brain of the same patient, l shall see any problems of lactate Lactate's very low in the micro dialysis probe, and I have plenty of glucose Head injury is regional It is not one organ

It happens differently at different parts You can have a concussion of a temporal lobe and not a concussion of the parietal lobe, okay? They would have different time frames, in terms of their recovery of function Well, maybe we ought to just give people a Snickers bar >> [LAUGH] >> When they come off the football field Maybe that's the reason we have such a lousy [INAUDIBLE]

I'm always watching the paper, looking for the scores, for the U&M football team I wonder why that is Then we ought to give him Snicker's bars Patients that come in with a head injury are typically hyperglycemic Meaning that there's a lot more glucose in their blood and mother nature does that

And we just wanted to know what happened in the brain when we gave these people serum in order to reduce the amount of glucose in the blood So here's a person that comes in with hyperglycemia That's around 300 We give them the start of insulin infusion And then the glucose goes down to normal, around 100 But look what happens in the brain, it goes to 0

We're starving the brain We're hanging the wrong thing on the IV bag Same with glucose metabolism and positron emission tomography that measures blood flow So say for instance we changed the serum glucose around a big range in normal people, well, blood flow stays pretty constant But look what happens in people with brain injury

All of a sudden they show ischemia, so they're not even getting the blood we're trying to give them Well, what about maybe it's not using glucose the same way? We'll take 1 mole of glucose, take it down a vessel,and have it drop down to a mitochondria And for 1 mole of glucose, Mother Nature needs 56 moles of oxygen Otherwise you get lactate

You get that burning of lactate I told you about That's called the oxygen glucose ratio In normal patients, or normal people, we'll have low glucose, lots of oxygen In head injury patients, we have hyperlycolosis And then we have something weird

We have very low glucose, but lots of oxygen being burned For matter of time, what does this look like when we do an image? Well, we'll take a glucose metabolism study and an oxygen metabolism study and we'll fuse them and we'll get an oxygen glucose ratio Well, I can explain low oxygen glucose ratio, that's when you're running up the stairs and you're making a lot of lactate I can't explain high oxygen glucose ratio, that means you're burning something else besides glucose Well, what on earth is there left to burn? So we decide to tag it

So we tagged glucose and acetate to see how it's being used in both neurons and in glucose cells And we found that in fact, the glucose isn't being used the same way And in human patients, what happens is that they're using the glucose to make things like proteins to turn on different types of proteins associated with DNA to help both repair process They're sparing their energy for this type of recovery as opposed to trying to make it so that it can work again So you can't get the fuel there

If you get it there, it's not being used for the same thing So people began to say, wow, this is really weird You got glucose that's being shunted out the wrong way, you got a lactate that's being used inappropriately, and you got other shuttles that go on This could be an opportunity though for metabolic therapy Maybe for the IV bag, maybe we should be handling, giving it some lactate

Maybe we should give it some pyruvate Or when you were children and when we were born, what you did is you burned ketone bodies Maybe we should give them beta hydroxybuterate and let the brain burn that Then we started to look at long term problems following concussion And what happened during the Afghan War and the war in Iraq is that they had this silent epidemic or this invisible wound called post-traumatic depression or post-traumatic stress disorder

Well, head injury doesn't give you post-traumatic stress disorder What happens when you have a head injury and your concussion, the first thing you notice is you have amnesia You can't remember If you're a psychologist and you will wanna know what post-traumatic stress disorder is, you perseverate on what you've seen You were there when the towers came down in New York

You were there when your buddy lost his limb You were there when somebody got shot in a school system That's what gives you post-traumatic stress disorder So, I designed a simple study, got together with Michael Fangslow And I said listen, what we wanna do, I wanna do some Pavlovian conditioning for fear conditioning

So we're gonna take an animal and we're gonna pair a sound and light to foot shock, so that the animal knows that if he hears this sound or this light, he's gonna get a foot shock And we're just going to look at the animal freezing We're gonna give him a concussion, and he shouldn't be able to learn this Lo and behold, when we gave them the concussion, not only did they learn it, they learned it faster Not only did they learn it faster, it was more unresponsive to therapy

Then in 1949, all of a sudden at King's College, this guy by the name of Critchley decided to coin this term called chronic traumatic encephalopathy And he did this because of soldiers that were under the effects of high explosives on the central nervous system I don't know how many of you are unfortunate enough to have a fired an M-16 or been next to a canon But it's like a pressure wave that comes back and moves you And they were worried that that's what was causing it

And it caused these long term effects Now we know, from all these studies that came in the press from the University of Boston, dementia, Alzheimer's disease, violence, psychological problems Even Lou Gehrig's disease, amyotrophic lateral sclerosis, this is Lou Gehrig, has been thought to be involved with this So we decided, well, you know something, let's get really smart Let's tag something that would be helpful in helping us identify Alzheimer's disease, or something that would be akin to that called tau, tauopathy

So we tagged it and we used it with five retired football players Gary Small did this study These are the five retired football players, and you can see the red areas are where the tau is, and now in the control, there's no tau Well, there are some problems here with validity and reliability and amount and rate So just this year, what happened is Amal had decided to join us

We ran the same study on an individual, was 61 years old, played professional football for 30 years And all of a sudden we got his brain, and the same tauopathy matched exactly where the signal was coming from in our pascoty We may be able to scan people and tell them, buddy, it's time for you to think about retiring Because you're gonna have this Now there's a recent paper that came out real recently that says that people over 60 and 65 begin to show this tau normally

This is part of the aging process, so it's still debatable On the left here, this is an automated modeling of 56 different regions of interest of the human brain So, we do this at UCLA, where we take these MRI images, and we've taken down Art Toga, who is now at USC, and we measured the volume of the brain Now, when you're born, the brain is small When you start to grow, the brain gets bigger

And the French were right Women's brains get bigger, mature faster than men's brains do And then once you get to be 40 The brain starts to get smaller and starts to atrophy And that's normal aging process So I took this particular image of an individual

And I took them to a neural radiologist and I overlayed the PET on it and I said can you just read to me and tell me what you think this is? He said this is an 82 or 85 year old person's brain I said this is a 22 year old staff sergeant that just came back from Iraq What about boxing? Boxing does this Well, we look at this tensor imaging You can see normal, so you can see all these fibers that we talked about

These axons, they look pretty healthy Here's a fighter that's been fighting for years, and look at the axons that start to drop off and that die because of this And for some reason, women have decided they wanted to become fighting And all the sudden we've got this thing called this cage fighting, have you ever seen that on TV? I tell you what, I've got some people at USC who I think should go into one of those things [LAUGH] And then we have one of these, and then what we decided is how you divide this up

If you take a bicycle wheel and you divide this into a left and a right hemisphere And you take all the different regions of the brain And you see the connections, and this is a normal individual And after a traumatic brain injury, all of a sudden, these areas start to get bigger or smaller, and the connections start to fall away And we published this a couple of years ago

I'm showing the uses, it's the same map that's used for genetics So what is TBI? It's an injury that's caused by a biomechanical force, it's not stroke, it's not ischemia It causes regional and temporal cellular alterations It can produce cell death It produces a state of energy crisis and subsequent metabolic diaschisis

We all now know what diaschisis is, i changes the priorities for fuel Listen people, we need to change our thinking here, this dex five is not cutting it It may be cutting it for the liver and the heart, because these are multi-trauma patients But it's not doing anything for the brain It can contribute to the acquisition of post traumatic stress and to chronic neurological degeneration related to different diseases

Maybe traumatic brain injury shouldn't be thought of as an event that you recover from Maybe it should be thought of as a disease that you're going to have to work with for a while In Jama on February 1st, 2018, just a few days ago When a sports related concussion is suspected, the athlete should immediately be removed from play And assessed by a physician or a licensed healthcare professional

When in doubt sit this person out When I work with the military or the athletes, I tell you the best person that can tell if somebody else has had a concussion is not the person that has had the concussion It's the person next to him that says something is different Tell coach, tell the athletic trainer, get that person away at least until he's stable enough to begin to exercise I'm just a cheerleader here, there's an immense team that has helped me over the years

And I am so grateful and they've done such a great job I hope if you ever get a chance to come to Los Angeles, I'm not in love with Los Angeles, I miss Albuquerque But UCLA is a beautiful campus and you are welcome to come by and visit Thank you very much for your attention and I'll answer any questions >> [APPLAUSE] >> I've got a bad back so if you don't mind I'm going to sit down

Not bad for 65? >> [LAUGH] >> Okay >> Doctor, is there a test for CT you got now? >> Yeah, there sure is As soon as you die I can get your head, I can get your brain out >> [LAUGH] >> I got this thing that will make you want to walk from here to Kansas and back >> Is there some way to be able to diagnose without having to die? >> No, I have to say no

The FDA has not approved it The ligand that we have, Pittsburgh has one as well, is working on it, to work with PET, positron emission tomography And not every hospital or university has a PET scanner, or a to make it What's important is that this tauopathy, or this tau, is a protein that's like the scaffolding that you would put on the outside of a build that you're gonna work on But it's on the inside of the cell

And so we all have tau What we're worried about is when it becomes it bends on itself Then all of a sudden the structure of the cell starts to get weird And as we start to have plaque entangles and that's called Alzheimer's disease,all right? If you just have tauopathy we now call that chronic traumatic encephalopathy So now we've got these two ligands that seems to be able to, enable us to see tauopathy

The problem is I don't know how much you need to have, to be clinically relevant And the second is I don't know why it moves Apparently, in people that we've studied, it seems to move It moves from the deeper part of the brain to other parts of the brain And I don't know why yet, we'd like to know why

And I would think, in about five or ten years, you're gonna be able to do, at least do more for what I call the stool of concussion The stool of concussion has got three legs First leg, do you have a concussion? The FDA just approved a serum test so I can actually do it on the sidelines and see if you've had a concussion according to the FDA >> Now, how long does that take to get the result? >> According to what they have told me on the press, minutes, I don't trust the FDA >> [LAUGH] >> There could be some dim light bulbs up there

[LAUGH] >> I'd like to see a little bit more of that data I saw some of it a year ago in Florida, and I was not impressed Because the signal to noise, it's great if you have a severe head injury I mean, if I put a hole in the brain, I see a lot of this S100B and this stuff in the serum I don't need that kind of a test for the whole

When Gabby Giffords got shot, there was plenty of that in her blood spray What I needed was somebody with a closed concussion, and that we don't know yet The second leg of the school is, when can I say to this athlete or this soldier, or this individual Okay you can go back in now, you can take another hit You can go back in and play

I do not have a good test that can definitively say when you can go back in to play I have to rely On the recommendations of both the Berlin conference and the Zurich conference, and the stepwise process that all the trainers are trained about They follow what's called the Zachary Lystedt Law, which I was involved with in the state of Washington Which states that, when you start them back into school, if they show symptoms then you take them back You should take them out to the, let them do some exercise

If they don't show any symptoms the next day, they can run around the track the next day And then finally they're clear, and they're about ready to go 80% of individuals, I was talking with the trainer at U&M here, just before my talk About 80% of the people clear in about fourteen days, after a single concussion Then there is this miserable minority, that seems to take months and sometimes years to recover

The third leg of the stool is when you tell somebody to retire You gotta stop, I'll never forget this, I was in Laguna Beach I was at a conference for concussion, and I'm supposed to give a talk about concussion, to these NFL players Linemen, and some quarterbacks I tried as hard as I could

And I don't mean this derogatorily, but I tried to keep the science down, and try to keep it matter of fact, that kind of stuff And I'm sitting at lunch and we have these sportswriters And I understand there's a sportswriter here from the journal, I thanked him for coming And they all wanted to talk to the quarterbacks, and the football players, Troy Aikman, and Steve Young, and Warren Moon And then this guy turns to me, and he's from the Dallas newspaper, the Dallas Morning News I think, sports writer

And at this particular time, the Raiders were still playing in Los Angeles, they were still the team in Los Angeles And Troy Aikman said that he had had nine concussions So the sports writer turns to me and he said, would you recommend, Dr Hoder, that Troy Aikman retire from the national football league? [LAUGH] >> I said, my job is not to tell Troy Aikman when he should retire from the National Football League My job, is to tell Troy Aikman what his chances are, or what he could get if he continues to get blows to the head, and plays in the National Football League

>> What were his chances? >> In my opinion, his chances of having long-term problems are gonna be 40% And he turns to me and he says, you don't get it, do you, doc? I said, what am I missing here? You don't know what it's like to play football in the National Football League And I said, no, I don't I played football in high school, Sandy High School, or Comanche Junior, I mean, middle school But I've never done a National Football League

He said, I would give up anything to play football I said, would you give up the ability to recognize your wife? Would you give up the ability to recognize your grandchildren? Would you give up the ability to feed yourself? And he said in a New York second I would do that And they all said that, and I don't know how to fight that And for when Paul Tagliabue was Commissioner, he had me speak to all the owners, and all the players physicians And, we all talked about the risks and stuff about concussion

And the owner say, we don't want to put this in the contracts, because the disability clauses is going to cost a lot of money And so then I went to the player's union, and I gave the same talk to the player's union And the players said no, concussion doesn't happen in the national football league I said what in the world, what is wrong with you guys Then all of a sudden he says to me, I was told

You know something, these guys are played on how much they, how, they get paid the amount of money how much they play If a doctor takes them out for a week, or two weeks of play, it can cost them a million dollars, it costs a lot of money Do you realise of much money is made on Monday Night Football? That is amazing, so I learned quite a bit, yes, ma'am >> Once you have the energy crisis and the cell, is there any way for the cells to recover? >> Yes, [COUGH] excuse me, in my professional opinion, when we've done this in animals and in humans Is that if we remove them from the field, whether there was a young woman that was playing lacrosse, and she got a concussion

Removed her from the playing field and went through the stepwise thing, and we let mother nature do what she wants to do And then we slowly began to work this individual back into play And then after about three or four weeks, she was fine She went back into play, she was fine So think about this for a second, teleologically, if we didn't recover from mild traumatic brain injury

Teleologically speaking, several thousand or million years ago, we would have been somebody's breakfast We wouldn't have recovered, we wouldn't have this ability, we've got this ability to recover We as scientists or as physicians, have just decided to kind of mess around with this a little bit And I've actually done a few things that maybe were a little bit wrong So when I started at UCLA, I turned to Don Becker and I said, Don, I don't think we actually know what happens following traumatic brain injury

I think all these things that people, that the pharmaceuticals want us to give to make money, they don't know either That's why nothing's working, we need to start from scratch Now, concussion happens to both men and women, women get concussions more often than men do But why is that? Well, one, one is that you have a different anatomy, to some degree So you got a smaller head, a supple neck so you get more violent movement of the brain

You also have this thing called hormones, that occur differently in different cycles of the month, and it depends on when you have your concussion, that's important So you actually respond differently Now, you complain more often of symptoms following a concussion than men do Now, in my personal opinion, not professional, but personal opinion, is that I just think women are more honest And I think the guys are just trying to cover it up, women will actually say, listen I'm not sleeping well, and I've got these weird dreams, that's the problem

There was a question back here first, to a guy in a hat, yeah? >> So it's not like concussions and brain injuries kind of in contact Experts I would say So what do you think is gonna be the future of such treatments, and is there anything to improve the situation at all? >> I think there's a lots of things to [INAUDIBLE] We have an example up here, the UNM football helmet, Kim? 1940? I don't know The leather ones

>> [INAUDIBLE] >> 30, or something like that And then we come up, and so the equipment is changing So we're getting better equipment The helmets, inside the helmet The helmets here are hard

There's a little give to it They're pretty hard A helmet doesn't stop concussion It doesn't stop it, but players come in, if it's designed properly, it can reduce the amount of acceleration and deceleration The rules have changed

So now you can't spear with this before I think that there are two kinds of sport There are sports where head injury is part of the goal of the sport Think of boxing The goal is to produce a concussion

Football, a concussion or field hockey, or soccer, or something like that, concussion's a byproduct, and as we increase their awareness of when these things happen, the rules may change, and yes we're going to reduce the amount of instances that it happens, but more importantly it's going to happen, regardless of what we do it's going to happen, but we're getting smarter to the point to we're now able to recognize it, and handle it So we're not having a Long for the Pittsburgh Steelers committing suicide, or driving his car over the edge because he's gone crazy, or the battered wives I think are going to go down I think we're going to improve that, because we're recognizing there's a problem It's now cool, I'll never forget this, there was a guy in Afghanistan, I led a mission with three guys to Afghanistan, it was called the Gray Team Three, and I was talking to a master sergeant, and E6 was helping me It's a corpsman, and he says, I've had a concussion, I get to sit out for two weeks

I had the same thing Jay Cutler had when he was playing for the Chicago Bears I've had a concussion Isn't that cool? 20 years ago, he would have kept that silent Yes, ma'am >> So in talking about, there's a lot of talking about how things happen and if there's any way of recovery, but is there experimental things out there that you're working with, or that you actually trust, or that might be helpful in this situation, and also, how long would it take for an experimental drug or method to come into play? >> Let me answer your last, let me ask your middle question first

I was a graduate student here at UNM It was 1979, and I was asked to give a lecture to the medical school class The first year medical school class, and I told the medical school class about this new thing that was coming out of Florida, out of the University of Florida, a colleague, that was called neurogenesis, that you were making new cells, and after their class, I was called into the Dean's office, and he said don't you dare lie to our students I said you've got to be kidding It's published in science

He says, no, no, no we're gonna make these students past the board The board exams are gonna say you don't make new cells So the boards needs to be changed, all right? You do make new cells Neurogenesis is one of those things I have hope for I'm not positive yet

Scientists are naturally skeptical I'm a skeptical person I'm not sure every tweet that comes out of the White House is accurate >> [LAUGH] >> I'm just naturally that way, all right? >> [LAUGH] >> I do think that there are things in the brain, I didn't get a chance to get into this cuz of time I didn't wanna bore you guys with boring things

There are these things in the brain called neurotrophic factors, or brain trophic factors, and so an example is, if you take, my brother's got four beautiful children If his oldest son, when his oldest son was two, or one years old, or two years old, three years old, and we dropped him over in Paris, I pick him up in about two months later, he's speaking French You take me over to Paris, you pick me up in three months, I can't tell you how to find out where the toilet is >> [LAUGH] >> There's a lot of plasticity in the brain We have just begun to tap it, and that has got great potential, and that comes, I can't give you B, D, and F

I can't give you [INAUDIBLE] factors, but you can make it, and I can show you how to make it, and I'm afraid to admit it, my wife is right I've been married 37 years My wife's always right I'm always wrong, exercise makes, the brain makes the factors from exercise Those are my big hopes

Yes >> Yes, I have a question about, you had spoken about the noise being a factor to concussion, like in war >> Yeah >> Those large martyrs What about the kinds of noise that we experience regularly in our lives, like going to the movie, going to a football game, where there's a blaring noise, how could that be a mild concussion? >> Good question

When a cannon goes off, it's instantaneous It's a loud, instantaneous blast If you go to a movie concert, or to a concert, and they do a blast, by the way, it's the same, it can shock you, okay? Usually though, in the theater or in a movie, concert, it's just loud, and your ears ring, and you get headaches and stuff like that I not, professionally now, I am not completely convinced that blast itself causes a brain injury I'm not convinced yet

I've seen the data and it's remarkable In the autopsies that I've seen, the brain damage is in the posterior inferior part of the brain I have no idea why it's there I know that people are different after they've been exposed to blasts My dad served in Korea, and they used to call it like blast syndrome, or concussion syndrome, and so I know people are different

I think what happens is that the blast causes what we now are starting to hear about, a sub-concussive blow A blow- >> Sub-concussive? >> Sub-concussive, which means it doesn't go through all of this stuff I'm telling you about, but it does make the brain a little more vulnerable So if his head gets hit again then it's a problem So in Iraq and Afghanistan I was surprised by the number of people that have concussions that are in a firefight You can't pull a guy out or a girl out during the middle of a firefight, they got to stay

What I was worried about is the people that are traveling there in an MRAP, and the MRAP hits an IED, and it gets rolled over There's seven people in the MRAP, which one has a concussion? I'd like to know that And that may be where the serum test comes in So maybe you would do that Yes sir? >> [INAUDIBLE] >> Two more questions

>> He's my boss, so I have to do what he says, sure >> Amateur boxing is doing away with headgear Fighters have to be sixteen and above, but the younger kids are still wearing them Pro boxing, of course, has never used them How effective, in your opinion, is headgear in preventing concussions in the body? >> None

Headgear is really good to stop contusions So if I hit you with the side of the head with a helmet, I'm sorry If I hit the side of your helmet with a hammer you're protected because the helmet is there But if I take, I always block on this guy's name He was a NASCAR driver, number 3

>> [INAUDIBLE] >> Yeah, yeah, yeah, yeah, yeah He died not because he was hit in the head but because his head was violently moved forward and back, he had a helmet on So now they have a harness, that they anchor in to the back So we could do that in players We could take the helmet, harness it to their shoulders so they can't move their head

>> [LAUGH] >> Maybe that's why I didn't play football very well >> [LAUGH] >> So that would start it There are studies now, today, I've been arguing for for many years I wanted people to look at the types of concussion and severity of concussions that you get in rugby, which doesn't have that kind of protection and in football That has protection

And, I'm hopeful that my colleagues in bioengineering, I'm not a bioengineer Has a way that will diffuse the force that would normally permeate the skull into the brain that would get diffused around the helmet and stop the concussion I'm hopeful of that I hated Bob Udall, the Udalls when they were in the centers There were a couple of companies that came out with helmets that they said stopped concussions and I was asked and I said no

Gave you the same answer And I looked at the data I said no Doesn't happen You can't make a statement And so they stopped making them

>> So doctor, [INAUDIBLE] as the last question, seeing as this is a local [INAUDIBLE] the majority of folks here are alumni And you as an alumni of the university of Mexico [INAUDIBLE] Could you wrap up or finish maybe with your experience and how you have impacted [INAUDIBLE] very very important military Of the department of defense and the impact that you have had and your work and your research has had on our United States military And you know the reason that you have that medal on your chest and why, You've been recognized in that way, how the military has been fundamentally changed when it comes to traumatic brain injury, removing the soldiers from the field

If you could just explain that to us, as an alum, certainly are certainly proud of you and that's something that is quite lasting >> I'll pay you later >> [LAUGH] >> I started I went to get my first grant and I went to a board, and it had all the deans of all the schools of UCLA, UC so UCLA, UC Davis, Berkeley, around the table, and the grant was being given by the Bank of California And on the other side of the table were all of the bank vice-presidents And at the other end of the table was the president of the bank

And I had this grant and I couldn't show any the slides, just tell them what the grant was about And the guy from San Francisco looks at my CV and he says, Dr Everett, we're very impressed with your application but there's something weird about your CV I said, what's that? He says, well you started college at the University of New Mexico in 1971 And you graduated in 1979

What happened? >> [LAUGH] >> And I said well I came home from school and after my third year and my dad says, son you are wasting your time, your grade point average is 18 >> [LAUGH] >> I know you are playing golf all over the place, I was playing golf You're having a great time, but this is a waste of time actually you are right dad it's a waste of time So I gave up school and I tried to play professional golf

I played one round of golf with Nancy Lopez and then I realized I can't make money doing this >> [LAUGH] >> So I went to the school of political science, and at the school of political science, I don't know where they are now, but they used to have a board And I'd close my eyes and I pointed And that guy, I went to his office with a tie on, my best looking shirt Knocked on the door and I said, all I need is somebody to sign a piece of paper letting me have one semester

Let me make grades and I'll stay And so after he heard my story, he signed the piece of paper and I stayed And I got on double secretive probation and then graduate school was the same way because my grade point average was 26 or something And Dr

Laney, who's sitting in the front row, he was grading one of my exams for statistics, and he's grades them blindly And he sees me in the hall and he says, is this yours? He says, yeah He says, you passed You can stay >> [LAUGH] >> So, and then they sent me to medical school here, and graduate school, and then of course I got my bachelor's degree, and then I went to UCLA for post doctoral degree

For the military, I built the National Traumatic Center of Excellence with colleagues that treat some mild traumatic brain injury and post traumatic stress And ten satellites, of which April the 4th I'm dedicating the eighth one to the military at Camp Pendleton I led a mission to Afghanistan to make sure that people were following the rules, in terms of taking players, players Wounded warrior's out of the field of battle I got a call when I was in Patrick's room from Admiral Mullen, when Gabby Giffords was shot

To take care of Gabby Giffords in Tucson I said I'm not gonna do that Gonna let the neurosurgeon take care of it because I knew the neurosurgeon and he does a good job And I put together two blue ribbon panels to help individuals understand at the joint chiefs level what concussion was and why individuals should be protected, both in garrison and in theater And then, Edward Mullen came by my office

He calls me and he says I want to have a secret meeting with you at UCLA I said Admiral Mullen you're the chairman of the joint chiefs of staff You show up on campus with four black sedans, it's gonna be really hard for me to the press quiet about this And so he shows up and he says, I got a mission for you And he explained to me this mission, we'd do this

And then he says, and by the way we wanna celebrate your career and in 2011 the United States Army has what they call the tattoo party, which is a parade party to celebrate the birthday of the army And every year, or every other year, they give the highest degree, highest award to a civilian from the army for their service to their country, and that's what this medal is from [INAUDIBLE] >> [APPLAUSE]

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