Brain scans of former NFL athletes show a repair protein in place long after initial injury

"The findings show that participating in repeated collision sports like football may have a direct link to long-term inflammation in the brain," says Jennifer Coughlin, M.D., associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. Ongoing studies like the current one, she says, add details about how the brain heals -- or doesn't -- and how repeated brain injuries, even mild ones that players routinely shake off, may over time affect cognitive abilities.

Coughlin notes that TSPO is a protein associated with immune cells in the brain known as microglia. This protein is always present at relatively low levels. When a person experiences a traumatic brain injury (TBI) of any kind, TSPO levels are greatly increased as part of the immune response. Past studies have shown the presence of elevated levels of TSPO up to 17 years after injury, which, researchers say, indicates the brain remains in a heightened state of injury and repair long after the traumatic event.

In the new study, researchers examined MRI and PET scans that were completed between April 2018 and February 2023 of 27 former NFL players. They compared these brain scans to those acquired from 27 non-collision sport athletes (swimmers) who all participated for at least two years in National Collegiate Athletic Association Division I, II or III level competition. All athletes were between 24 and 45 years of age, and all were male. All participants in both groups underwent cognitive assessments, including memory tests.

Results show that former NFL players performed worse in learning and memory tests than the swimmers. Additionally, they found that levels of TSPO in the former NFL athletes were higher on average compared with the swimmers, particularly in areas of the brain associated with memory and attention.

"These findings are relevant to both collision sport athletes and other populations that suffer from single or reoccurring mild TBIs, including those experienced during military training and repeated head banging behaviors in children," says Coughlin. "Since TSPO is associated with repair, we don't recommend the use of drugs or other interventions at this time. Instead, we will continue to monitor TSPO levels through more research, in order to test for sign of resolution of the injury with more time away from the game."

Coughlin stresses that if there are cases where TSPO remains high, researchers will study those factors that associate with a vulnerability to lasting injury after a professional career in American football. Ultimately, they aim to guide strategies for the use of immunomodulating treatments (possible anti-inflammatory medications) to heal the brain when needed.

Researchers say they plan to continue to follow the study's population of former NFL athletes to track TSPO levels over time to see whose brain heals and whose does not. The goal is to inform development of medications and personalized guidelines for rest periods after repeated brain injuries.

The new research adds to a growing stack of evidence that collision sports that involve repeated, even low-level, blows to the head, including football, soccer and boxing, may lead to dementia and other forms of cognitive disorders.

Other scientists who contributed to this research are Mary Katherine Brosnan, Robert Dannals, Yong Du, Andrew Hall, Daniel Holt, Jessica Kilgore, Wojciech Lesniak, William Mathews, Il Minn, Hwanhee Nam, Riley O'Toole, Martin Pomper, Steven Rowe, Leah Rubin, Laura Shinehouse, Gwenn Smith, Ana Soule, Shannon Eileen Sweeney, Cykyra Thomas, Mark Yoon and Adeline Zandi of The Johns Hopkins University; Samantha Bureau and Michael Burke of the Concussion Legacy Foundation; Christopher Nowinski of the Concussion Legacy Foundation and Boston University; and Michael Kassiou of the University of Sydney.

Christopher Nowinski is a volunteer member of the Mackey-White Committee of the National Football League Players Association, for which he receives travel support. He is also an adviser and options-holder with Oxeia Biopharmaceuticals, LLC, PreCon Health and StataDx; has served as an expert witness in cases related to concussion and CTE and is compensated for speaking appearances and serving on the Players Advocacy Committee for the NFL Concussion Settlement; and is employed by the Concussion Legacy Foundation, a 501(c)(3) nonprofit that receives charitable donations from the public. All other authors have no conflicts of interest to disclose.

This research was supported by the National Institutes of Health.