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Understanding the Effects of Blasts on the Brain


By: Veterans Health Administration, Research & Development Dept.

It's a scientific question driven by the hard realities of today's global war on terror: What happens to the brain of someone exposed to a blast?

The answer is likely to come not from the battlefields of Iraq and Afghanistan, but from research labs thousands of miles away—such as that of biomedical engineer Pamela VandeVord, PhD, with VA and Wayne State University in Detroit. She is one of a small but growing number of researchers studying the biological effects of blasts on the brain.

 With funding from VA, VandeVord's team studies brain cells that have been exposed to "overpressure" in a lab device called a barochamber. The investigators dial up or down the pressure and control its duration.

VandeVord: "If there's an explosion, there's a shock wave. But once it gets transmitted to your brain, it's not a shock wave anymore. It's a high-speed compression wave. We are generating that compression wave in the barochamber. It simulates what we believe occurs in the brain."

The goal is to learn how the cells respond to different levels of blast injury. The researchers look at whether cell membranes get damaged, for example, or at what point cells ultimately die.

VandeVord also has funding from the Office of Naval Research (ONR) to conduct animal studies of mild brain injury. Whereas the VA study focuses on cells, the ONR project focuses on tissue. The findings from both will give a fuller picture of the biology of brain injury.

The Defense and Veterans Brain Injury Center estimates that from 10 to 20 percent of troops serving in Iraq or Afghanistan have suffered some type of brain injury. Most of the injuries are considered mild— but even many of these cases will involve permanent cognitive and emotional problems that can tear apart the lives of veterans and their families.

Much of the ONR-funded phase of VandeVord's work takes place in a large, open space equipped with a 22-foot-long metal shock tube. The back end of the device—the driver—forces a sudden burst of air down a long cylinder, simulating the pressure wave of an explosion. The researchers wear ear protectors and wait in a separate, Plexiglas-enclosed room when the blasts rip through the tube.

Inside the shock tube are brain cells suspended in gelatin, or rats. The blasts range in size from 5 to 20 pounds per square inch (PSI)—small by comparison with typical roadside bombs. But the blasts are scaled down for testing on rodents. Depending on the duration of exposure, a lethal dose of overpressure for a rat would be around 35 PSI.

"We're trying only to induce mild brain injury," says VandeVord. She says using animals is the only way scientists can learn what might be happening in human brains. "We're at a critical point in the research, and we can't practice on people. We have to go through these steps and optimize what we can before we can get approval to try something in humans."
 
The pressure wave from roadside bombs and other improvised explosive devices (IEDs) can cause traumatic brain injuries for troops even when they are many feet from the source of the blast and suffer no other physical injuries.

Research may lead to therapies for combat zones
Based on findings from both the VA- and ONR-funded work, VandeVord and colleagues will aim to design therapies that can be administered in the combat zone to troops—either before they go out on patrol, as a preventive measure; or after a blast has occurred, to stem damage to the brain.

According to VandeVord, in more severe injuries, brain cells die and the damage is more likely to be irreversible. In milder brain injuries—including many instances where soldiers or Marines are many feet away from the blast and suffer no visible wounds—cells may not die, but they do get damaged. Says VandeVord: "A lot of the guys with mild TBI can recover in six months' time. What is the point where the cells will die, and what is the point where the cells can still repair themselves?"

Figuring out the relationship between the power and distance of a blast, and the exact effects on brain cells and tissue, is her focus right now.

Studies include genetic component
Some of the lab rats undergo post-blast brain scans using a rodent-sized MRI machine. Others undergo blood tests in which the scientists look for proteins, released by injured cells, that could be biomarkers of brain injury. This may lead to a blood test that military medical personnel could give to troops immediately after a blast to determine if they are physically OK or if there is subtle damage.

"We're hoping this can translate to the soldiers," says VandeVord. "If we find something that's in the blood, it could enable doctors to do a quick test to see how much damage has occurred and then administer therapy accordingly."

The rats also undergo cognitive testing before and after the blasts. The researchers hope to correlate changes in memory to the level of blast exposure and to specific changes they are seeing in the rodents' brains.

"We use a maze," explains VandeVord. "We do several training periods and we see how long it takes the rats to perform a task. Then we test them after the blast to see if it takes them longer."

Through both the VA-funded cellular work and the ONR-funded animal studies, VandeVord's team also hopes to learn which genes get activated in brain injury. Figuring out a way to turn off those genes with a drug could spell a breakthrough for the treatment of brain injury on the battlefield and in field hospitals.

"When the brain is exposed to overpressure from a blast, we believe there's a cascade of negative events that occurs, and this is set in motion by certain genes that get turned on," says VandeVord. "If we can learn how to stop the expression of those genes with some type of pharmacologic agent, we can stop this cascade of events within the brain and possibly limit the damage."
 
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