Article published November 25, 2007
Team at University of Toledo tackles brain injury puzzle
Troops in Iraq prone to affliction
Col. Geoffrey Ling, above, heads a Defense Department program on traumatic brain injury.
Damir Janigro, at right, theorizes that ultrasonic forces in blasts are behind such injuries.
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UNIFORMED SERVICES UNIVERSITY
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By JENNI LAIDMAN
BLADE SCIENCE WRITER
For generations, explosives have made warfare ever more deadly, killing, crippling, and disabling with impersonal capriciousness.
Now, a group of researchers at the University of Toledo wants to take some of the harm out of the bomb.
Maria Coleman, a chemical engineer at UT, is leading a team of engineers, physicians, and experts in the human brain to come up with ways to prevent, diagnose, and treat the so-called "signature" affliction of the war in Iraq: traumatic brain injury.
In Iraq, damage from blasts has taken a new turn. While improved body and vehicle armor allows servicemen to walk away from explosions in greater numbers than ever, they're often later found to have brain damage.
"Honestly, we are victims of our own success," said Col. Geoffrey Ling, who leads a research program on traumatic brain injury for the Defense Advanced Research Projects Agency (DARPA), the research arm of the Department of Defense.
"Many of these soldiers get knocked out for a minute or two, brush themselves off, get up, and go on," said Col. Elspeth Cameron Ritchie, the psychiatry consultant to the U.S. Army surgeon general, speaking at a mental health forum last year. "These soldiers return home with mild traumatic brain injury, and often become irritable or have difficulty concentrating. People close to them may think it's just [post-traumatic stress disorder]. It could be the effect of a head injury," Dr. Ritchie said.
Team member and UT bioengineer Scott Molitor,
left, with graduate student Mark Skopin, is testing the response of brain cells — neurons — to electromagnetic pulses, which are among many components of an explosion.
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THE BLADE/DAVE ZAPOTOSKY
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Ms. Coleman's focus is prevention. Her hope is to help create armor that can shield soldiers from whatever is causing the damage of traumatic brain injury. She has worked with the military in the past developing protective materials with polymers and nanofibers and knows it's possible to make materials that can shield from electromagnetic pulses, pressure waves, and more. But at this point, it's not certain just what damage soldiers need to be protected from. No one knows what causes traumatic brain injury.
That's why engineering assistant professor Mohammad Elahinia is making a bomb - a virtual one that will exist only on 128 networked computers.More than a noise
A bomb, it turns out, is more than flying shrapnel and loud noise. There's the pressure wave that knocks down everything in its path and pulsing ultrasonic waves, rushing electromagnetic impulses, increasing heat, and a mix of chemicals.
Mr. Elahinia's mathematical model will include all of these, as well as just what happens to individual neurons caught in the blast, work that UT bioengineer Scott Molitor is engaged in. He already is testing the responses of neurons to electromagnetic pulses.
Once this model is complete, Ms. Coleman's creations can be tested and improved upon using the model.
Damir Janigro theorizes that ultrasonic forces in blasts are behind such injuries.
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CLEVELAND CLINIC
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Head injuries from this war are overturning many of the assumptions about brain damage, Dr. Ling said. Traumatic brain injury patients at Walter Reed Army Medical Center were examined with magnetic resonance imaging and computerized tomography, and neither scan found the traditional signs of brain injury expected in, say, automobile accidents or falls.
Many thought that pressure waves from explosions were behind this puzzling damage, but DARPA-contracted studies seem to disprove that supposition, Dr. Ling said.
In this work, pigs were exposed to explosive blasts. They weren't blown through the air. They weren't hit by shrapnel. But the experimenters found evidence of brain injury.
"They were having a hard time walking and a hard time feeding themselves," Dr. Ling said. Postmortem examination of their brains showed degenerated nerve fibers.
To see if it was the pressure wave that was to blame, pigs were exposed to pressure waves from an air cannon.
The pigs proved hard to injure this way.
In fact, the pigs showed no signs of brain injury until the air cannon pressure was 10 times greater than the pressure wave from an explosion, Dr. Ling said. "That means obviously there's more to this than pressure."
The DARPA research program is designed to consider all possible causes of brain injury.
"An [improvised explosive device] is a very dirty environment," Dr. Ling said.
"Yes, there's pressure waves … [but] other things in the environment may be contributing to why these biological organisms, particularly our soldiers, are getting hurt."
He tells researchers: "I don't want you to take an assumption that they're hurt because of X Y Z. Doing so would commit a lot of folks to making erroneous assumptions," he said. "Make no assumptions."Breaking sound barrier
Damir Janigro of the Cleveland Clinic Foundation, and a member of the UT-led team, is betting that it's ultrasound that's behind the brain damage, and that's part of the problem he works on.
He theorizes that ultrasonic waves are causing a leak in the special architecture of blood vessels supplying the brain. Vessels in the brain are lined with nearly impervious cells. Although capillaries in the rest of the body are designed to leak, allowing an easier passage of cells and chemicals into tissues, brain vessels allow only very controlled entry of limited substances, such as glucose.
A rat model of head injury in the 1990s showed that this blood brain barrier leakage accompanied neuronal damage or behavioral change, Mr. Janigro, director of cerebral vascular research at the Lerner Research Institute, said. Later, reports of human injuries from Israel and Germany seemed to indicate the same vulnerability, he said.
The blood brain barrier is known to be vulnerable to ultrasound. In fact, researchers at a variety of institutions are experimenting with ultrasound to deliver drugs to the brain for things like cancer treatment, he said.
Mr. Janigro is now looking at the impact of ultrasound in a laboratory system, in which cells are tested in a simulated blood vessel environment for their response to ultrasound.
If Mr. Janigro's insight proves accurate, it may hold a key for early diagnosis of traumatic brain injury.Identifying injury fast
A simple, battlefield diagnosis is an issue of particular concern for the military, said Lt. Col. Michael Jaffee, the national director of the Defense and Veteran Brain Injury Center.
"One of the challenges … is looking for a true-blue, objective biomarker to help us identify someone," Dr. Jaffee said.
Mr. Janigro thinks he has two promising candidates for such a field-test biomarker. His research uncovered two proteins that show up in the bloodstream when the blood brain barrier is breached.
The proteins were found by conducting blood tests on people whose brain tumors were treated by creating permeability in the blood brain barrier.
Also high on Dr. Jaffee's wish list for traumatic brain injury victims is finding a quick and effective method of treatment.
Dr. Thomas Papadimos of the University of Toledo Medical Center, the former Medical College of Ohio, hopes that nitric oxide may hold promise for treatment.
Dr. Papadimos, an anesthesiologist, acknowledges that his hopes for nitric oxide are based on some fairly limited findings, beginning with his own experience with a head injury patient who was also suffering from acute respiratory distress syndrome and high intracranial pressure - his brain was swelling.
"He wasn't doing very well at all," Dr. Papadimos said. "He wasn't given much hope."
He decided to try nitric oxide, which can temporarily rescue patients in respiratory distress.
The nitric oxide made the patient's lungs better, as expected, but, it also seemed responsible for drop in intracranial pressure.
"Three weeks later, he was in a rocking chair watching TV. That should not have happened," Dr. Papadimos said.
"I thought it was a fluke, maybe dumb luck," he said. Then he found two more cases of similar successful treatments in the medical literature. He said he can't help wondering how many times nitric oxide was used unsuccessfully and not reported, but still, the finding seemed to beg further study.
He's applied for a grant to try nitric oxide on comatose patients.
The gas, which costs $100 an hour to administer, would be given to 100 comatose patients with concurrent chest injury. Then, physicians would look for any effects on intracranial pressure, brain oxygenation, brain temperature, and cardiovascular function.Promising treatment
Progesterone is another promising compound for the treatment of brain injuries. A small study published in the Annals of Emergency Medicine compared 77 traumatic brain injury patients administered progesterone with 23 patients given a placebo.
Thirty days after the injury, the death rate for the progesterone group was 13 percent, while 30 percent of placebo patients died. The positive effect was strongest for those with moderate injury.
But for Dr. Papadimos, with 24 years' military affiliation - he retired in 2001 - the big concern is that someone, anyone, find a solution for these service people. It doesn't matter so much if he does.
"I don't care who has the answer," he said.
"I'm just concerned. I want people to make these guys better," he said. "I'm hoping someone comes up with an idea, a theory, a way to treat and diagnose."
Contact Jenni Laidman at:
jenni@theblade.com
or 419-724-6507.
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