Therapeutics
Background
Repeated head impacts in contact and collision sports are associated with an increased risk of long‑term brain disorders, including chronic traumatic encephalopathy (CTE). However, CTE can currently only be diagnosed after death, and there are no reliable tests to identify people at risk while they are still alive. This has made it difficult to understand how repeated head injuries lead to progressive brain damage years after playing stops.
Scientists have increasingly suspected that damage to the blood–brain barrier (BBB)—a protective layer of blood vessels that normally prevents harmful substances from entering the brain—may play a central role. What has remained unclear is whether BBB disruption can persist long after retirement from sport, and whether it is directly linked to cognitive decline and neurodegeneration.
Research
A team of researchers, including FutureNeuro investigators, examined brain health in retired athletes with long‑term exposure to repetitive head impacts. Using advanced brain imaging (dynamic contrast‑enhanced MRI), blood analysis, and postmortem brain tissue, the researchers studied 47 retired athletes from collision and combat sports and compared them with non‑contact sport controls.
The study revealed that BBB disruption was still present many years after retirement, indicating that damage from repeated head impacts may be a chronic, ongoing process. A distinct subgroup of retired athletes showed widespread BBB leakage across large areas of the brain and performed significantly worse on cognitive tests, particularly those measuring memory and executive function. These individuals also had lower brain volumes compared with those with little or no BBB disruption.
Blood analyses showed ongoing immune activation in these individuals, particularly involving the complement system—part of the body’s immune defence—linking vascular damage to inflammation. Examination of postmortem brain tissue from individuals with confirmed CTE further demonstrated BBB leakage and immune activity around damaged blood vessels, strengthening the link between vascular dysfunction, inflammation, and neurodegeneration.
Potential Impact
This study provides strong evidence that persistent blood–brain barrier disruption can be detected years after repeated head trauma and is closely associated with cognitive decline in a subset of retired athletes.
By identifying BBB damage and immune changes that can be measured during life, these findings open new possibilities for earlier detection of trauma‑related brain disease risk. They also point to potential therapeutic strategies focused on vascular repair and immune modulation, rather than targeting brain cells alone.
Together, this work represents an important step toward developing biomarkers that could support earlier diagnosis, improved monitoring, and more targeted interventions for individuals exposed to repetitive head injury—well before irreversible neurodegeneration has occurred.
Read the full publication here
