TBI Sets Off Response Similar to MS In Brain

A new study suggests an intriguing new take on concussions: That the brain damage found in professional football players may be caused by an out-of-control immune response, similar to what multiple sclerosis patients experience.

http://www.urmc.rochester.edu/news/story/index.cfm?id=3767

Research by the University of Rochester Medical Center (URMC) and the Cleveland Clinic, published in the journal PLOS ONE, suggests that perhaps a vaccine or drug can be created to prevent brain damage, based on the work’s findings, a press release last week from the Rochester school said. The brain illness du jour NFL players is chronic traumatic encephalopathy (CTE).

Emphasizing that the research is preliminary, study co-author Dr. Jeffrey Bazarian, associate professor of Emergency Medicine at URMC, said its theory fits with the reality of what experts have observed among athletes.

He worked closely with lead investigator Damir Janigro, professor of Molecular Medicine at the Cleveland Clinic, and 67 college football players from northeast Ohio and Rochester, N.Y., who agreed to participate in the study.

“Although the awareness of sports-related concussions is much higher, we still know very little about the long-term consequences and what happens inside the brain,” Bazarian said in a statement.

“Our theory is plausible as an explanation for how routine head hits that come with playing football can lead to severe neuro-degeneration later in life,” said Bazarian, a national expert who has served on an Institute of Medicine committee for brain injury. “If others confirm this, it could present options with drugs that influence the immune response.”

It all hinges on the blood-brain barrier, a semi-permeable gate between the brain and bloodstream.

“No other organ has such a barrier,” the press release said. “When the barrier is working properly, it holds in proteins and molecules that bathe the brain and protect it from foreign substances. With blows to the head, however, the barrier opens slightly and allows some proteins to leak into the bloodstream.”

Scientists discovered that S100B, a protein biomarker for TBI, was present in varying degrees in the blood samples of the 67 football players after every game — even though none of them suffered a concussion.

This demonstrates that even the most routine hits have some impact on the blood-brain barrier and possibly the brain itself, Bazarian said in the release.

In this research, scientists wanted to find out what happens after S100B moves from the brain into the bloodstream.

“Again, they made an important finding – that the body views S100B as an enemy and begins to form antibodies against it as if it were a virus,” the press release said. “Researchers hypothesized that a buildup of antibodies would result in a more vigorous attack on S100B in the bloodstream.”

But something unexpected was discovered.

“Some antibodies sneak back through the damaged blood-brain barrier to the brain and begin to harm the healthy brain cells that produced the S100B protein in the first place,” the release said. “This is analogous to a missile searching for a target, Bazarian said, with some unintended targets eventually falling under attack.”

The S100B accumulates in dendric cells, the regulators of auto-immune responses. So as the blood-brain barrier repeatedly opens during the football, researchers theorized that it might set the stage for a continuous autoimmune-type attack on the brain.

“In multiple sclerosis a similar breakdown occurs, when the body’s own immune system damages myelin sheaths around the brain,” the release said. “Other health conditions that harm the blood-brain barrier include sepsis (overwhelming infection), burns, critical illness, or seizures.”

In order to test the hypothesis, blood samples were taken of each player before and after games. Scientists analyzed the samples for S100B levels and auto-immune antibody levels. They also tracked the number of hits each player sustained by viewing game films and conducting post-game interviews. They also gave each player cognitive and functional tests, pre-season and post-season.

In addition, a subset of 10 players from the University of Rochester received special brain scans with diffusion tensor imaging, a sensitive MRI that can detect subtle axonal injury.

And the findings?

Players with the most head hits also had the highest S100B levels and elevated levels of autoimmune antibodies. Players who often remained on the sidelines had significantly lower S100B levels. In addition, the blood samples predicted abnormalities seen in the imaging tests, and correlated with observed cognitive changes.

Although many scientists are actively investigating concussions in the United States right now, it’s been difficult to study the link between brain injury, blood-brain barrier damage, and the long-term risk of neuro-degeneration because of a lack of simple, non-invasive tools, Bazarian said.

But demonstrating that S100B can be used in this way adds a new dimension to the scientific literature. Other investigators have also used the S100B protein to study Alzheimer’s patients, the study noted.

According to the press release, Bazarian is banking that at some point S100B “will be a tool for emergency rooms and other clinical settings to screen for concussions. Doctors can accurately measure it with a simple finger prick; many European countries already use S100B to decide which patients need a CT scan when a concussion is suspected.”