Research into Blast Injury and the Brain
Using animal models in the lab to study the mechanisms of blast-related brain injury, researchers like Dr. Lee Goldstein are feeling optimistic that their findings will lead to viable treatments.
In the second part of the study we wanted to look at the mechanisms that subserve the relationship between blast and injury to the brain. There's been quite a bit of research done in this area. We kind of started this in another fashion. We modeled our experimental blast on what our military servicemen and women see in the field. We modeled this actually on 120mm artillery round IED, so the common IED that was encountered in Iraq. It packs punch, about 5.8kg of TNT at 5 meters, so it's not a firecracker. This is a very serious weapon and has done a lot of damage to a lot of people. A lot of our servicepeople live now because their lungs are protected. They wear Kevlar vests, and that has actually permitted a lot of these folks who are exposed, our servicepeople who have been exposed to these type of weapons to actually survive. So we built an experimental blast that modeled that. And, importantly, we protected the chest and allowed the head to be able to move in the setting, just like our military servicepeople. When we did this, to our surprise, we found that in these really ordinary laboratory mice that after a single exposure these same mice started to develop the same neuropathology that we see in humans. We were actually shocked to see this. We were expecting to only be able to do this in special mice, but lo and behold, we actually saw pretty much the same pathology that I just described to you, early CTE, in these mice after 2 weeks after exposure to a single blast and with very little differences from what we see in people. Not only did we see the pathology, but we also saw the tau accumulation, and we saw the microvasculopathy that I just described. We also saw the damage to the axons. But we saw changes in the physiology of the brain. The electrical properties of the brain changed. The nerve conduction was slowed down tremendously, and the ability to learn and to remember were also severely impaired. And even the electrical connections between neurons that enable them to talk so that we can learn and remember were seriously impaired and chronically impaired. We were not expecting that. It also appeared to us--our results suggested--these injuries do not resolve. And in fact, at least in the time period of the study that we conducted the study, they appear possibly to progress and possibly get worse. So that was quite alarming to us. We don't know yet whether that will continue to be the fact or whether these injuries will ultimately resolve over months or years, but it did raise our concern that after a single blast that there could be chronic damage that potentially progressed. We asked the question, what is it that causes the injury? And it turned out quite differently than we expected. We thought it would be the blast wave going through the brain, and when we measured this, sure enough, the blast wave does go through the brain. It does so in microseconds, and it does so with very little damage. What's behind the shock wave is a blast wind, and the blast wind, even for a modest explosive device like this, can whip around at 300, 350 miles an hour and it goes back and forth. If you think about putting your hand out of a car going 80 miles an hour down the highway and you stick your hand out, you're going to have quite a push back on your hand as you stick your arm out. If you bring that up to 350 miles an hour and you oscillate that back and forth over a period of milliseconds, you will unlikely have an arm attached to your body. And that's pretty much what we saw here. We call this the bobblehead effect because the head really does bobble on the neck in this setting, and that's what causes the damage. In fact, when we held the head still, we did not see the long-term neurobehavioral deficits that we saw when the head swung. So that gives us tremendous confidence that we're onto the right mechanism. And, importantly, that gives us tremendous optimism that we can now intervene.
Posted on BrainLine February 28, 2013.
Dr. Lee Goldstein is an associate professor of Psychiatry, Neurology, Ophthalmology, Pathology and Laboratory Medicine, and Biomedical Engineering at the Alzheimer's Disease Center at Boston University.
Produced by Brian King, Vicky Youcha, and Erica Queen, BrainLine.