Cell Death Versus Cell Survival
When I was young, everybody in my field--or most people in my field were very interested in how to stop cells in the brain from dying after a traumatic brain injury. And there was a concept many, many years ago about excitotoxic events, so that once the brain was jostled it would release these neurotransmitters. And one of them was glutamate; it would cause the excitotoxic cell death. And people would describe that there was a critical window of time when you wanted to intervene and stop this cell death process. It was very popular from a scientific perspective. And then out of that grew this concept of apoptosis and programmed cell death and then also what we call autophagy, which is a way of a cell actually causing death itself. And it happens in development all the time. And I thought that a novel idea was that I'm not interested in what happens to the cells that die. I think we can try to work on that. I'm interested in what happens to the cells that survive. How do I make them more plastic? How do I have a 5-year-old or a 4-year-old or a 3-year-old that has a devastating head injury that does so much better than somebody who is 25 years old or 30 years old? How can language shift from one hemisphere to the other after a major--why does that happen? How can I make that happen? And so to do that we began to study models of mild injury because we didn't want to induce cell death. We wanted to see what would happen to cells that were exposed to a biomechanical load. In severe head-injured patients, we would put our probes or our scientific interests not in the contusion but in the areas that were still surviving. So, inadvertently we had these models of "concussion" that we were studying. There was a gentleman by the name of--when the National Football League was run by Paul Tagliabue, many, many years ago, and there was a guy who owned--he was the agent for Troy Aikman, Steve Young, Warren Moon, yeah. And he was down at Newport Beach in California, and he had heard about this concussion issue. And he heard me give a talk with a gentleman by the name of Jose Sulaiman. Jose Sulaiman is the president of the World Boxing Council, and Jose Sulaiman was very, very worried that the World Boxing Council wasn't doing enough to protect its fighters or to recognize concussion or to stop a fight or how do you protect a fighter in between? How long should they stay out after they have been--their bell was rung? And so we started talking to them about this, and it wasn't so much that people didn't think something happened, because they could see in people's eyes, or in boxers we knew dementia pugilistica--for many years, punch-drunk syndrome. But for the NFL and for those types of sports, they didn't understand how much of this was psychological, meaning players were just not sucking it up or they had lost the enthusiasm for competition, and how much of this really was a neurological event induced by this dysfunction. In the early '80s, we began to find ways to actually give them a picture of the human brain and how it responds following a concussion. And all of a sudden, once they saw that this picture showed physiology, and then people sat back and said, "Yeah, there is something going on, and there probably is a reason for it to be--to take a player out." But people don't realize that effort started in the 1990s, and it wasn't until 2009 that the National Football League came out with an official statement that concussion was part of the National Football League. And I was overjoyed when that happened because I knew that that would trickle down to college sports and to high school sports, and it would trickle over to different areas like the military, where kids didn't want to be taken out of the battle or taken out of the field. But if Cutler had to take 2 weeks off for the Chicago Bears because he had a concussion, now it was cool to have a concussion and have to stay out. And it protects them a lot better for that. So it was more serendipitous in how I got involved with concussion. I never really--it wasn't my plan. But it was the idea of looking at what happens to these cells that are exposed to injury that don't die.
Researcher David Hovda, PhD is less interested in aptosis — or cell death — after TBI than what the cells that survive are doing to compensate for what is lost.
Posted on BrainLine October 18, 2011.
David Hovda, PhD is the director of the UCLA Brain Injury Research Center. He is past president of the National Neurotrauma Society and past president of the International Neurotrauma Society. He has served as chair of study sections for the National Institute for Neurological Disease and Stroke.
Produced by Noel Gunther, Ashley Gilleland, and Brian King, BrainLine.