New Study Investigates Long-term Impact of Non-concussive Brain Hits in Football Players

There have been numerous studies regarding the long-term consequences of concussions in athletes, a study published March 6, 2013, in the online journal PLoS ONE now takes a closer look at the potential long-term affects of repeated, non-concussive head hits in football players. The study was a collaborative effort of the University of Rochester Medical Center (URMC) and the Cleveland Clinic and was sponsored by the National Institute of Neurological Disorders and Stroke (NINDS).1

non-concussive-head-injury-300x200A broad goal of the researchers was to support the theory that there are long-term consequences associated with non-concussive head trauma experienced by athletes. Study co-author Jeffrey J. Bazarian, M.D., M.P.H., associate professor of Emergency Medicine at URMC, notes that the research is preliminary, but he is excited that this theory seems to fit with observations seen by experts who have observed brain-related health issues in athletes. “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,” Bazarian said.2

Damir Janigro, Ph.D., professor of Molecular Medicine at the Cleveland Clinic, worked as the lead investigator on the research. The team studied 67 football players from northeast Ohio and Rochester, N.Y., who agreed to participate in the study. Players were given cognitive and functional tests prior to the football season and then again afterwards. They also provided blood samples before and after each game, and researchers tallied the number of head hits each received by reviewing game tapes and conducting post-game interviews. In addition, brain scans that utilized diffusion tensor imaging were conducted on 10 University of Rochester players.1

The S100B protein biomarker and blood-brain barrier roles

The team focused on the presence of the S100B protein biomarker in the bloodstream during their research, since it is a commonly accepted indicator of traumatic brain injury. The researchers discussed how S100B is released into the bloodstream when the player’s blood-brain barrier is compromised during a concussion, and they wanted to determine if non-concussive head trauma would also show elevated levels of S100B. 1

The purpose of the blood-brain barrier is to act as a “semi-permeable gate between the brain and bloodstream. When the barrier is working properly, it holds in proteins and molecules that bathe the brain and protect it from foreign substances.”2 If the barrier is compromised, proteins such as S100B can be released into the bloodstream.

During their research, the research team discovered that players who endured repeated non-concussive head hits during a game, consistently demonstrated elevated levels of S100B post-game – even though they didn’t experience a concussion. The more hits they experienced – the higher the levels of S100B that were found to be present.

Could an autoimmune disorder result from brain injury?

This is another question the research team hoped to answer. The National Institutes of Health estimates that 80 or more human diseases result from an autoimmune response, afflicting more than 10 million Americans. Common examples of these include multiple sclerosis, rheumatoid arthritis, lupus and type 1 diabetes. In a healthy body, we have mechanisms that help fight off harmful microorganisms such as viruses, parasites and bacteria. An autoimmune disorder occurs when the body gets confused and attacks healthy cells. 3

In the URMC/Cleveland Clinic study, the researchers found that when S100B was released into the bloodstream, the body treated it like a virus and formed antibodies to fight against it. They also found that healthy brain cells were being attacked when these antibodies seeped back into the brain through the compromised blood-brain barrier. 1

Along with finding higher levels of S100B in the players who experienced the most hits, and lower levels in those who spent more time on the sidelines, the researchers were able to predict abnormalities that showed up on the imaging tests by analyzing the blood test results. Bazarian hopes that more research will result in better screenings for concussions by testing blood samples for S100B and lead to the development of brain treatment at an earlier stage. If a simple blood test can help diagnose traumatic brain injury, hopefully cost savings will follow. 2


1. Marchi N, Bazarian JJ, Puvenna V, Janigro M, Ghosh C, Zhong J, Zhu T, Blackman E, Stewart D, Ellis J, Butler R, Janigro D. “Consequences of Repeated Blood-Brain Barrier Disruption in Football Players.” PLoS ONE, 2013; 8 (3): e56805 DOI: 10.1371/journal.pone.0056805. Available at Accessed March 14, 2013.

2. “Study Suggest New Way of Thinking about Brain Injury – As Autoimmune Disorder.” March 6, 2013. University of Rochester Medical Center website. Available at Accessed March 14, 2013.

3.  Johns Hopkins Medical Institutions, Autoimmune Disease Research Center, website. Available at Accessed March 13, 2013.


Keywords: brain injury, traumatic brain injury, concussion, brain treatment

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