What can mice teach sports about concussions?

LAB PHOTOS BY SIMON BRUTY/THE MMQB

BETHESDA, Md. One of the most important recent developments in the treatment of brain traumaand by extension, the future of footballmay have been discovered by a clumsy intern.

Theo Rothisa St. Louis-born, Alabama-raised Stanford graduatewho finagled his way into a National Institutes of Health internship in the summer of 2010, after his senior year of high school. Bored after graduation, he appealed to Dr. Dorian McGavern with a personal email and the recommendation of a mentor of his parents, both doctors. McGavern, new at the NIHs suburban Maryland health campus, allowed the 18-year-old to sidestep the pool of more than 10,000 college kids gunning for 1,000 spots and took him on. McGavern and his team were using a new research tool, pioneered in 2007 at New York University, which involved shaving down a small portion of a mouses skull to shine light into the brain and record its processes. McGavern wanted to study how meningitis affected the brain, but his new intern couldnt handle the tiny ballpoint saw without concussing the mice and muddling the results.

He was really bad at performing skull-thinning surgery, McGavern says of Roth. Just couldnt get the hang of it.

It wasand remainsa difficult thing to accept for a kid who scored 35 out of 36 on his ACTs and 2350 out of 2400 on his SAT. Its really hard to do, and they only gave me a week to learn, Roth says of the procedure. They have neurosurgeons come in and get it wrong.

Mouse after mouse wasconcussed, but something valuable did come of the process. Roth and McGavern observed in the subsequent images of the rodents brains a flurry of actionleakage from blood vessels lining the skull seeping down and causing brain damage. Towards the end of the summer, the twostarted talking about what they had seen in the concussed mice. Roth, a former high school wrestler and a Rams fan, connected the dots. We saw the brain operating in ways no one had ever recorded before, and right around the same time, traumatic brain injury was becoming a hot topic, Roth says. People were starting to realize how detrimental it was in the NFL and for guys coming back from Iraq and Afghanistan.

Roth and McGavernwere chatting one morning in the cramped computer roomin McGavernslab when something clicked. It was like, wait a minute, were actually recreating what happens in a mild traumatic brain injury, Roth says. This may actually be very important.

The wheels started spinning. It became Roths personal project to study concussed miceafter all, he was the best in the lab at injuring them. Rather than take his time while sawing down the skull, Roth buzzed through the process in 45 seconds, shaving the bone from a density of one millimeter to 30 microns, about the width of a human hair. The anesthetized mouse was then strapped under a two-photonmicroscope, a four-foot tall machine that allows for imaging of living tissue. Over the rest of the summer and the summer after that, the bright blue, green and purple images relayed to the computer gave McGavern and his team an outline for the mechanism of damage from minor head trauma. Heres a thumbnail of what happens:

McGavern believes this process could play a fundamental role in the development of chronic traumatic encephalopathy (CTE), the disease that has been found in the brains of deceased former football players. CTE has shown up in the autopsied brains of former Bear Dave Duerson and former Charger Junior Seau, both of whom committed suicide. Its also listed as evidence in the case made against the NFL by thousands of former players who sued over decades of alleged mistreatment of concussions by NFL doctors. CTE and the concussion epidemic are the reason the NFL agreed last year to pay $765 million to those players, plus $30 million to the NIH to fund studies on the biggest problem confronting football at all levels of the game.

But the NFL wasnt funding this project. This was an NIH undertaking being performed by a researcher whose main interest was viral infection and an intern with shaky hands and a special mind. Roth became obsessed. He wentto Palo Alto with mice on his mind. He joined the marching band, and it became his distraction, but as soon as winter and spring breaks began, he was on a plane to the East Coast. I was much more excited to be doing the research than I was to be taking classes, he says. It was a little rough to be studying for a midterm when I was thinking about the next experiment we could do. I was doing work that was brand new, as opposed to learning things from a book that people already learned long ago.

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What can mice teach sports about concussions?