Concerns about the long-term impact of repeated head impacts in young people continue to grow worldwide, particularly in countries where contact sports are culturally significant, such as the United States. A recently published scientific investigation sheds new light on the early biological alterations that may occur in the brains of individuals exposed to frequent head trauma.
Repeated cranial injuries, common in sports such as American football and football, military service, and accidental falls, are known to increase the likelihood of developing chronic traumatic encephalopathy (CTE). This progressive neurodegenerative condition has been associated with cognitive decline, behavioural disturbances, impulse control problems, mood alterations and difficulties with memory and communication. To date, however, a definitive diagnosis can only be made post-mortem through microscopic evaluation of brain tissue.
Examining Subtle Brain Changes After Repetitive Trauma
A research team led by Dr Jonathan D. Cherry at Boston University, United States, examined tissue samples from 28 men aged 20 to 51 years to better understand the cellular changes that precede CTE. The samples included individuals who had never practised contact sports, athletes who had taken part in sports such as football or American football without meeting the diagnostic criteria for CTE, and a group diagnosed with early-stage CTE. The findings were published in Nature in August 2025.
Across all athletes involved in contact sports, the scientists observed a range of cellular alterations—even in those who did not show the defining markers of CTE. One of the most notable findings was an increased presence of inflammatory microglia, immune cells that act as the brain’s first responders following injury. The group also identified modifications in gene expression affecting cerebral blood vessels, further signalling the impact of repeated head trauma on vascular function.
A striking discovery was the 56% reduction in neuronal density within specific grooves of the brain's surface in athletes who had experienced repeated blows to the head. Moreover, this loss correlated with the duration of exposure to contact sports, indicating a possible cumulative effect.
Neuronal Loss May Precede Classic CTE Pathology
The hallmark of CTE is the accumulation of a protein known as p-tau around blood vessels in deep brain folds. However, the researchers found no correlation between p-tau levels and the extent of neuronal loss. This suggests that brain cell degeneration may begin much earlier than the deposition of p-tau—one of the major insights of the study.
The team then explored the molecular communication pathways involved in these changes. They identified TGFB1, a signalling molecule produced by microglia, which appears to play a significant role in coordinating cellular responses following repeated head injury. Differences in TGFB1-related signalling pathways were also noted between athletes with early-stage CTE and those without the condition, even though both groups had practised contact sports.
Implications for Prevention and Future Research
The researchers emphasised that larger studies are necessary to verify these findings and to deepen the global scientific understanding of the mechanisms that trigger CTE. Still, the results underline an important warning for families, coaches and sporting organisations:
“These findings highlight that even athletes without CTE can experience significant brain injury,” Dr Cherry noted. “Understanding how these changes develop—and how to detect them during life—will be crucial for improving prevention and treatment strategies aimed at safeguarding young athletes.”
The growing body of evidence from the United States and other countries reinforces the need for continued monitoring, early detection tools and stricter policies around head injury management in youth sports. As participation in contact sports remains popular worldwide, developing effective protective and educational measures will be essential to reducing the long-term health consequences faced by the next generation of athletes.