News Release

Study finds risk of brain damage in college football players, even among those without concussions

Blood tests before, after games measured biomarkers for brain injury

Peer-Reviewed Publication

Cleveland Clinic

Wednesday, March 6, 2013, Cleveland: Concussions are the leading cause of brain damage in sports, particularly in football. However, researchers at Cleveland Clinic and the University of Rochester have found that football players may suffer long-term brain changes even in the absence of concussion.

In a study of 67 college football players, researchers found that the more hits to the head a player absorbed, the higher the levels of a particular brain protein that's known to leak into the bloodstream after a head injury. Even though none of the football players in the study suffered a concussion during the season, four of them showed signs of an autoimmune response that has been associated with brain disorders.

"Much attention is being paid to concussions among football players and the big hits that cause them, but this research shows that more common, 'sub-concussive' hits appear to cause damage too," said Damir Janigro, Ph.D., the director of cerebrovascular research in Cleveland Clinic's Lerner Research Institute, who led the study in collaboration with Nicola Marchi, Ph.D., of Cleveland Clinic and Jeffrey Bazarian, M.D., M.P.H., of the Clinical and Translational Science Institute at the University of Rochester Medical Center.

The study – published March 6, 2013, in the online journal PLOS ONE and sponsored by the National Institute of Neurological Disorders and Stroke (NINDS) – incorporated several methods to assess brain injury, including blood tests, brain scans, and tests to measure memory, motor control, reaction time, impulse control and balance, in addition to extensive review of game video to assess head hits among the players in the study.

For the blood test, researchers drew blood from football players at Baldwin Wallace University, John Carroll University and the University of Rochester before and after games, in order to search for the S100B protein in the blood. (Of the 67 players in the study, 57 underwent blood tests. Pre-season baseline levels of S100B were measured in 27 players.)

Typically, S100B is found only in the brain; finding S100B in the blood indicates damage to the blood-brain barrier. While the exact function of S100B is not known, it is used in many countries to diagnose mild traumatic brain injury when other typical signs or symptoms are absent. Studies in Janigro's lab revealed that once in the bloodstream, S100B is seen by the immune system as a foreign invader, triggering an autoimmune response that releases auto-antibodies against S100B. Those antibodies then seep back into the brain through the damaged blood-brain barrier, attacking brain tissue and leading to long-term brain damage.

Four players – out of the 27 for whom pre-season S100B blood levels were measured – showed signs of an autoimmune response to S100B, which has also been associated with other brain disorders, such as epilepsy and dementia. Brain scans (using diffusion tensor imaging) confirmed that the presence of S100B antibodies in the players' blood correlated with brain tissue damage, comparable to what one typically observes in the scan of a whiplash victim.

"Think of the blood-brain barrier disruption as opening a door to the brain that shouldn't be open," Janigro said. "Proteins like S100B that normally stay inside the brain get out where they aren't supposed to be – and get attacked. In addition, the door is open for things that don't belong in the brain to get in."

Estimates suggest that up to 40 percent of football players experience a concussion annually, the majority of these going unreported. Overall, the U.S. Centers for Disease Control and Prevention estimates that 3.8 million Americans suffer concussions each year.

Concussions can be difficult to diagnose, relying on player symptoms, cognitive tests or CT scans or MRIs that cost thousands of dollars. The S100B blood test offers an objective measure of whether a player has endured head trauma, as the researchers found that elevated S100B levels directly correlate to the number and severity of head hits. Body contact or simply playing in a football game did not affect S100B levels in the players.

A blood test will be much less expensive (about $40) and could be performed anywhere, such as locker rooms or doctors' offices. More importantly, though, the blood test could offer a yes-or-no determination of whether an athlete requires medical intervention as a result of in-game collisions.


This research – supported by a $250,000 grant from NINDS, part of the National Institutes of Health – can be found on PLOS ONE's website at

The S100B blood test is one of several projects Cleveland Clinic is undertaking to better detect and prevent brain injuries across a wide range of sports, including football, boxing, hockey and soccer. Teams of researchers are working to make safer youth football helmets (through a grant from NFL Charities), to create an Intelligent Mouthguard that measures the number and severity of hits to the head among athletes, and to develop an iPad app that uses the device's built-in gyroscope to quantitatively capture pre- and post-game measures of balance, memory and cognition. In Las Vegas, the Cleveland Clinic Lou Ruvo Center for Brain Health has launched a landmark study with professional fighters that will help determine whether MRIs of the brain, along with other tests, can detect subtle changes in brain health that correlate with impaired thinking and functioning. The research teams draw from their experiences of caring for thousands of professional, amateur and youth athletes every year on the sidelines and in clinic.

About Cleveland Clinic

Cleveland Clinic is a nonprofit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S.News & World Report consistently names Cleveland Clinic as one of the nation's best hospitals in its annual

"America's Best Hospitals" survey. About 2,800 full-time salaried physicians and researchers and 11,000 nurses represent 120 medical specialties and subspecialties. Cleveland Clinic Health System includes a main campus near downtown Cleveland, eight community hospitals and 18 Family Health Centers in Northeast Ohio, Cleveland Clinic Florida, the Lou Ruvo Center for Brain Health in Las Vegas, Cleveland Clinic Canada, and opening in 2013, Cleveland Clinic Abu Dhabi. In 2010, there were 4 million visits throughout the Cleveland Clinic health system and 167,000 hospital admissions. Patients came for treatment from every state and from more than 100 countries. Visit us at

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