Study Finds Some Immune Responses Decrease After Repetitive Head Trauma and During Early CTE

While previous research from Boston University’s Chronic Traumatic Encephalopathy (CTE) Center has shown that the connection between repetitive head trauma and CTE may occur partly though elevated neuroinflammation, a new study has found that the type of immune response that occurs in early CTE is not uniform and that some aspects of it might be impaired and decrease after injury.

The researchers also found that in individuals who have a history of contact sports but have not yet developed CTE, there are specific metabolic impairments that are found in the area in the brain where CTE pathology is first seen.

“Fully understanding the brain’s complex response is necessary to untangle the advantageous versus disease causing components of the brain’s inflammatory response following repetitive head trauma,” said Thor Stein, MD, PhD, a neuropathologist at VA Boston Healthcare System, associate professor of pathology and laboratory medicine at BUSM and co-corresponding author of the study.

CTE is a degenerative brain disease associated with a history of repetitive head impacts, including those sustained in contact and collision sports such as American football and boxing. At this time, CTE can only be diagnosed after death through a neuropathological examination of brain tissue.

In order to investigate how genes are affected in different brain regions by contact sports participation and CTE, the researchers studied brain tissue from two different brain areas taken from three groups: individuals who had no exposure to contact sports, individuals with exposure to contact sports but no diagnosis of CTE, and individuals with early, low stage CTE. The two brain areas studied were 1) the region where CTE pathology is first observed and 2) a closely neighboring region that is only affected in more advanced, severe disease. The researchers analyzed the genetic signals that act as messengers to make certain proteins and compared them across each group. By observing what was changed in the first brain region but not the second, they identified genes that are related to contact sports participation and early CTE pathology.

According to the researchers, this work furthers the understanding of the mechanisms of CTE. “While we knew neuro-inflammation was important in early disease, we didn’t know the specific pathways involved. This work gives us more clues to the type of neuro-inflammation so we could possibly design more targeted therapeutic treatments,” explains co-corresponding author Jonathon Cherry, PhD, a research health scientist at the VA Boston Healthcare System and assistant professor of pathology and laboratory medicine at BUSM.

“Additionally, the identification of metabolic changes prior to the development of CTE suggests metabolic dysfunction might be an early change amenable to treatment.”

This study appears online in the journal Free Neuropathology.