Boosting the blood-brain barrier could avert brain damage in athletes

Frequent head impacts in sports can lead to long-term harm to the blood-brain barrier, potentially contributing to chronic traumatic encephalopathy (CTE), a degenerative brain condition observed in some footballers, rugby players, and boxers. Currently, CTE is diagnosed post-mortem, but this discovery could pave the way for new methods of diagnosis, prevention, and treatment.

“There are many drugs in development that are seeking to restore the blood-brain barrier for the treatment of neurological disorders, so the future will be very bright if we can see the approval of some of these medications,” says Matthew Campbell at Trinity College Dublin in Ireland.

Campbell and his team examined the brains of 47 retired athletes from contact sports like football, rugby, and boxing, who had stopped playing an average of 12 years ago. They also looked at athletes from non-contact sports such as rowing and individuals with no sporting history.

Participants received an MRI contrast agent that infiltrates brain tissue only if it breaches the blood-brain barrier, which normally prevents harmful substances from entering the brain from the blood. In 17 retired contact sport athletes, the contrast agent was visible in multiple brain regions, indicating severe blood-brain barrier damage. In contrast, the agent was barely detectable in those who hadn’t played contact sports.

Athletes with more severe blood-brain barrier damage also scored lower on cognitive and memory tests, suggesting that such damage may be an early indicator of CTE, characterized by cognitive difficulties, memory lapses, depression, and mood instability. Michael Buckland at the University of Sydney in Australia notes that previous evidence of blood-brain barrier disruption aligns with this finding, reinforcing the connection.

Chris Greene from the Royal College of Surgeons in Ireland explains that head collisions and whiplash in sports cause mechanical damage to the blood-brain barrier. This barrier, often likened to a wall, is more accurately described as a dynamic system composed of tightly packed cells lining brain blood vessels. Impact forces loosen the seals between these cells, increasing permeability.

When the barrier is compromised, proteins, immune cells, and inflammatory substances in the blood can enter the brain, causing inflammation and damage. The research team also found evidence of immune cell infiltration and blood proteins in the brains of deceased CTE patients. CTE shares similarities with Alzheimer’s disease, which some researchers believe is also driven by a weakened blood-brain barrier allowing harmful substances into the brain.

Similar to Alzheimer’s, CTE involves an abnormal accumulation of the protein tau in the brain. Normally, tau is a structural protein in neurons, but head trauma can cause it to misfold and become disorganized.

When head injuries damage the blood-brain barrier, blood proteins and inflammatory substances can penetrate the brain, exacerbating tau misfolding and aggregation. This process, according to Greene, eventually leads to the cognitive changes observed in CTE. Buckland and his colleagues previously found that brains of deceased CTE patients showed gene signatures linked to blood-brain barrier issues, supporting these findings.

Currently, CTE diagnosis is only possible post-mortem through the identification of abnormal tau accumulation in the brain. However, Campbell and Greene suggest that their MRI method could help diagnose living individuals showing cognitive and mood symptoms. In the future, this imaging technique might also assess CTE risk in active athletes, though more research is needed.

Greene believes that if blood-brain barrier disruption is an early factor in CTE, drugs that strengthen or repair the barrier could potentially slow or prevent the condition’s progression. Bevacizumab, a drug that reduces blood vessel leakiness, could be worth exploring, alongside other anti-inflammatory drugs like minocycline, which are also under development.

“Instead of waiting until tau pathology is entrenched, we may be able to intervene earlier by protecting the vasculature, reducing harmful blood-derived signals and calming the inflammatory cascade before it becomes self-sustaining,” says Greene.