Science Interviews


Thu, 7th Mar 2013

Rethinking Head Injuries

Dr Jeffrey Bazarian, University of Rochester Medical Centre

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For most professional rugby or American football players, repeated knocks to the head are considered an occupational hazard. But over the course of their carrier, they can result in long term damage. Now, scientists have developed a new theory that means that there might be more we can do to protect players beyond fitting them with a helmet. To  find out more, we were joined by Dr. Jeffrey Bazarian from the University of Rochester Medical Centre and started by asking we used to think happened when people were subjected to repeated blows to the head.

Jeffrey: Well, weíve only begun to actually see a connection between these repeated blows and something bad happening. People think if there's something bad happening that it involves stretching these long spaghetti-like cells in the brain, the neurons, so causing the axonal damage, just in doing that repeatedly in a low level over and over, over again. So, the thinking has been that the damage kind of builds up with time, some critical threshold is reached and they get dementia later in life.

Chris: So, itís just because if you keep on shaking the head too hard, you're going to sever nerve cells axons, these connections and eventually, you're going to lose cells, lose connections, and this will have a cognitive decrement.

Jeffrey: Thatís exactly right. 

Chris: So, what are you saying is different?

Jeffrey: Well, it looks like the problem, might be not so much with injuring the American Footballbrain cells, but injuring the gate between the brain and the blood - this barrier called the blood brain barrier. The brain is kind of a funny organ thatís walled off from the rest of the body by this barrier and itís normally closed.

Our study suggests that these blows to the head that we donít think about being bad repeatedly open up that barrier and allow proteins that bathe the brain to get out into the peripheral circulation which doesnít sound so bad. But the main discovery here is weíve found antibodies. The body actually makes antibodies to those proteins so the next time that gate opens up, that antibody is looking for a target. Itís like a heat seeking missile looking for a target and where does it go? It goes back to the cell that made the protein to begin with, back into the brain across this breached blood brain barrier and we speculate, that may be part of the process of this long term nerve degeneration.

Chris: What evidence have you got that a.) the blood brain barrier is opening up in that way when there is head trauma or repeated trauma and b.) that those antibodies are then actually going across the blood brain barrier later and doing damage?

Jeffrey: Excellent question. So, the first question you posed was actually more easy to demonstrate, but using this blood test called S100B, this a protein thatís made by astrocytes in the brain. Itís not found anywhere else. So, the blood barrier has got to be open for this stuff to show in the serum. We can't actually visualise the blood barrier in someone who is alive. You can only do it post mortem. So, this is a kind of a surrogate measure of blood barrier patency and if you see this protein above a certain level, the blood brain barrier is open and we kind of establish some of those thresholds in prior studies. So that part was easy. Showing antibodies to the protein, that was easy.

Your second question now is much harder to prove. We can't actually see these antibodies on living brain tissue. There's no way to kind of image that in someone whoís alive. If they were willing, we could take a piece of their brain out, look at it under a microscope but most folks who play football aren't really interested in doing that. So, we have to do some work with animals. We took the blood from some of these athletes that have the antibodies, poured it over mouse brain and saw that itís stuck to the cells that we thought expressed this. Itís a leap to say, well, itís probably happening in the human, but we saw it in the animal, so it makes the connection easier to make, but by no means, causative.

Chris: What is it going to take to prove this, now that you have this intellectual leap and youíve got some evidence that certainly the antibodies are being made and can we stop it?

Jeffrey: I think thatís why we probably have to turn to animal models. You know, how you establish causality in these cases as you do the typical things. You try to block the antibody response, see if the brain injury is prevented, you try to stimulate the antibody response, see if you get more brain injury, you sacrifice the animal, look to see if the antibody is sticking to the cells in a more direct way. In the humans, itís going to be really difficult to prove that link unless somebody could come up with a non-invasive way to image these antibody complexes on the brain.

Chris: What about professional footballers? Are we going to see them being told, ďWhatever you do, donít head the ball in the future because you could get brain damageĒ?

Jeffrey: Thatís a little different question. I think there's a lot of people, myself included, trying to tighten that connection, trying to show that whatever happens acutely with this subconcussive head blows that they somehow are directly linked to neurodegeneration, 10 or 15 years later. Thatís kind of difficult to do because of the time involved, but I think we need to connect a few more of those dots before we start telling footballers to not hit 70, 80 times a game.

Chris: But how hard do you think you have to hit your head in order to get this effect or is it really rather trivial head trauma that will do this?

Jeffrey: Thatís exactly the kind of things that need to be established. Luckily, with the invention of centres accelerometers for helmets for football players, we can start to answer what exactly, what threshold needs to be reached before we start to see some Ė either an immune response or some microscopic brain injuries. So, that work is being done. Itís harder to do in rugby players or in soccer players because we can't really measure the forces to their head without them wearing some kind of sensors on their head. They donít wear helmets, so that makes it harder to do. But there's many people who are on hot on the trail of this question.


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