The Blasted Brain

Traumatic brain injury (TBI), the signature injury of the current U.S. wars, calls for the nation's best "emergency medicine," Kevin Kit Parker told a group of top scientists, medicine makers, and policy makers, this spring at the One Mind for Research conference in Boston.

"Certainly TBI, as it affects the force, is a national security issue, and it's certainly an emergency issue." Like the race to the moon and the Manhattan project, he said, TBI is an emergency science project with national security at stake and a need to move rapidly.

"You've got young NCOs [non-commissioned officers], young soldiers out there that have been blown up a dozen times, a dozen times they've suffered a traumatic brain injury, since 9/11. We have this growing cadre of our professional warriors that are out there, that are walking around, and the concern is, what does the future hold for them?"

The timelines of TBI damage range from nanoseconds to years. "The data now is pretty clear that TBI can potentiate a variety of neurodegenerative diseases, including Parkinson's and Alzheimer's disease," Parker said. "So the outlook for these young soldiers is kind of bleak right now."

Parker, a professor at Harvard, has also served multiple tours in Afghanistan in the Army Reserve, tending the wounded immediately after impact and observing their recovery on base and back in the United States. The experiences led him to expand his research focus from the physics of the heart to the brain. "When people started trying to kill me with IED's I thought I'd better get a piece of this," he said.

His background also led to an unusual approach to the problem, or at least unusual for neuroscientists. "I'm an infantry officer in the reserve, and I'm not a physician, I'm a physicist, so I look at things in terms of scaling laws." Interested in how mechanical energy (such as from blasts) affects neurons, he and the people in his lab decided to try to build physical models of blast injury from molecule to cell and from cell to tissue.

"We use tissue engineering as a tool, including blasting neurons," he said. "What we found right away is that we can mimic some of the things that the neuropathologists are reporting that they're seeing in patients."

"Now that we've got all these models, we're working on developing a systematic understanding of the mechanical forces required to injure these neurons, these vascular tissues, and understand the chemical cascades that are turned on by these mechanical forces." If they understand these chemical cascades, they could start to identify which molecules along the cascade are the most vulnerable—and which might be easily reached by drugs and other therapies.

Part of emergency medicine is exploring many avenues simultaneously, Parker said. His theory is it's diffused axonal injury that leads to damage from TBI, but researchers need to work on multiple hypotheses, to "flank the problem" with the outside-the-box ideas until someone finds some badly needed solutions.

One giant challenge: "We need to build a brain," he said. "Everyone would benefit from having a brain in their [laboratory] dish to work on:" a 1 mm3 piece of brain that mimics the neural microenvironment, scalable so what people discover in the lab can be tested in drug-maker's wide-assay studies. He's working on it.

In addition, "we need to push the science as far forward [on the battlefield] as we possibly can," he said. "It might be a diffusion tensor imager that we put downrange, it might be a biomarkers lab that we put downrange … so we can understand, as these soldiers come off the battlefield, what's happening to them, rather than waiting 6 months, 12 months before they present at a VA emergency room."

"The whole idea is that when these guys [medics] run up there to pull these broken kids out of this MRAP [armored vehicle], that there's a whole team behind them supporting them," he said. "If I run up there and this kid's got a leg dangling off, I know how to apply a tourniquet to him. If I run up there and he's got his bell rung, I got no way of treating this guy right now. And right now he's at the genesis of these neurodegenerative diseases that might not appear for 20-30 years down the road."

His remarks start just after minute 1 of this video. The slides he uses are especially useful in understanding the science.

The forum was held in Boston May 23–25 by the One Mind for Research campaign, whose goal is "to significantly reduce the U.S. burden of disability due to brain disorders." The campaigners released a blueprint of research goals at the event: "A Ten-Year Plan for Neuroscience: From Molecules to Brain Health" (PDF). Videos of all the sessions are collected on the Science Network site.

The Science Network also did a wide-ranging interview with Parker, on work in the lab, his experience in Afghanistan, how he got started in science, and his passionate advocacy for his compatriots in the field. (22 min). It's also well worth a listen.

–Nicky Penttila

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