Hits to Head May Spur Brain-Damaging Immune Response

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Frequent hits to the head, which commonly occur during football games, are known to put people at risk for later brain disease, and a study published today  offers a new explanation for why this might be.

After a subconcussive blow to the head — one that is not severe enough to knock a person out — the body's immune response, rather than the blow itself, may be responsible for destroying brain cells, the researchers said.

The researchers hypothesize that hits to the head open up the blood brain barrier — a "gate" between the blood and the brain that typically stops substances from getting in and out. Once open, a protein found in the brain called S100B can leak out. Because the body is not used to seeing this protein in the blood, it may develop antibodies to it. The body produces antibodies to fight what it perceives to be a harmful substance. If these antibodies then find their way back into the brain, they could cause the body to attack itself, the researchers say.

In a study of 67 college football players, the researchers found that blood levels of S100B were indeed elevated during the hours after a game, but only in players who had sustained repeated hits to the head. Levels of antibodies against S100B were also elevated in the players who'd had frequent head hits. Those with the highest antibody levels tended to score lower on postseason tests of balance and cognition.

"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 study researcher Dr. Jeffrey Bazarian, an associate professor of Emergency Medicine at the University of Rochester Medical Center.

However, Bazarian cautioned that the study results are preliminary, and further research is needed to confirm them. Right now, the researchers do not have proof that antibodies against S100B find their way back to the brain — a critical part of the hypothesis that needs confirming.

The findings do not necessarily apply to people who experience concussions as a result of a hit to the head, as none of the participants in the study had suffered a concussion.

Earlier studies have found that football players, boxers and military veterans have signs of the brain disease chronic traumatic encephalopathy, or CTE, on autopsy. Previously, it was thought that this disease  was caused by the physical damage that occurs as a result of repeated hits to the head over time.

But if the damage is really caused by an out-of-control immune response, there may be ways to prevent it with, for example, drugs that block the development of S100B antibodies, Bazarian said.

The new findings are intriguing and "something that really ought to be explored further," said Dr. John Hart, medical science director at the Center for Brain Health at the University of Texas at Dallas, who was not involved in the study.

Hart noted that the study only shows an association, not a cause-effect link. It could be that this is just how the body reacts to hits to the head. Studies that follow athletes for many years will be needed before we know if the presence of S100B in the blood, and S100B antibodies, are linked to the development of actual brain disease, he said.

The study is published today (March 6) in the journal PLOS ONE.

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