Damage to the blood-brain barrier is linked to immune changes and cognitive decline
By Max Kozlov & Nature magazine
Repeated hits to the head over years of contact sports can lead to chronic brain damage.
Blake Little/Getty Images
For decades, scientists have struggled to understand exactly how years of being hit in the head while playing sports can result in severe memory loss and dementia later in life.
However, a study published today in Scientific translational medicine reveals that the protective shield known as the blood-brain barrier can become damaged and leak decades after an athlete retires from the sport. According to the study, this persistent escape appears to trigger a long-lasting immune response closely linked to cognitive decline.
This is a “very important study that reveals disruption of the blood-brain barrier several years after head trauma,” says Katerina Akassoglou, a neuroimmunologist at the Gladstone Institutes in San Francisco, California, who was not involved in the research.
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Lasting damage
Part of the difficulty in studying the long-term effects of head trauma is that some neurodegenerative diseases, such as chronic traumatic encephalopathy (CTE)), can only be diagnosed by examining neuronal tissue after death, explains Matthew Campbell, a specialist in neurovascular genetics at Trinity College Dublin, co-author of the article.
Campbell and his colleagues wanted to see if they could detect warning signs in living athletes by observing the blood-brain barrier, a dense layer of cells lining the blood vessels that supply the brain. This layer generally prevents harmful substances from escaping the blood and entering brain tissue.
To investigate, researchers scanned the brains of 47 athletes who had retired from contact sports with a high risk of concussion and repeated head impacts, such as rugby and boxing. They also looked at a control group of non-athletes and athletes who played non-contact sports.
Brain scans showed that the blood-brain barriers of contact sports athletes were significantly tighter than those of people in the control group, even though the athletes had been retired for an average of 12 years at the time of the study. People with the most damage to the barrier performed worse than those with less leakage on memory and cognitive tests, the researchers found.
“This is the first evidence in the living human brain that the blood-brain barrier is disrupted in individuals at risk for CTE,” says Campbell.
Difficult diagnosis
Standard blood tests used to detect brain damage were not very effective at identifying people with cognitive decline, researchers found. Instead, the warning signs only became visible after the team examined the athletes’ immune systems: The blood of people with the greatest barrier damage and greatest cognitive decline contained a higher proportion of inflammatory white blood cells and other biomarkers of immune activation than the blood of those with less damage. “It seemed like athletes were systematically living in a hyper-inflammatory state,” says Campbell.
This finding suggests that brain scans detecting leaky vessels could one day serve as a tool to identify living patients at high risk of serious brain diseases, the authors write. It also gives scientists a potential target to develop treatments to prevent this type of neurodegeneration.
These findings shouldn’t dissuade people from participating in organized physical activity, Campbell says. “Exercising is incredibly healthy for the brain,” he says. “This type of damage we’re seeing is due to prolonged exposure – it’s the cumulative nature of head trauma that is concerning.”
The researchers then hope to replicate their results in a larger population. Campbell says the study included few women – just seven of 62 athletes and control participants combined – because, at the moment, there are far fewer retired elite female athletes than male athletes.
This article is reproduced with permission and has been published for the first time March 18, 2026.
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