Understanding the effects of blasts on the brain
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."
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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