A new study co-authored by a Boston University School of Public Health (BUSPH) researcher has identified evidence of early Chronic Traumatic Encephalopathy (CTE) brain pathology after head impact — even in the absence of signs of concussion. Early indicators of CTE pathology not only persisted long after injury but also spread through the brain, providing the best evidence to date that head impact, not concussion, causes CTE.
The findings, published online in the journal Brain, are based on analysis of human brains from teenagers with recent head injury and mouse models that recreate sports-related head impact and military-related blast exposure. The investigators also performed laboratory experiments and computer modeling. Study results shed light on the origins of CTE and relationship to traumatic brain injury (TBI), concussion and subconcussive head injury.
In the first part of their study, the researchers examined four postmortem brains from teenage athletes who had sustained closed-head impact injuries one, two, 10, and 128 days prior to death. Neuropathological analysis of these brains showed a spectrum of post-traumatic pathology, including one case of early-stage CTE and two cases with abnormal accumulation of tau protein. Brains from four age-matched athletes without recent head injury did not show the pathological changes observed in the head-injury group.
To investigate causal mechanisms underlying these changes, the researchers conducted laboratory experiments using mouse models of two different injury mechanisms — repeat closed-head impact and blast exposure — both linked to CTE. The investigators compared brain responses to the experimental injuries and relationship to CTE pathology over time.
“The same brain pathology that we observed in teenagers after head injury was also present in head-injured mice. We were surprised that the brain pathology was unrelated to signs of concussion, including altered arousal and impaired balance, among others. Our findings provide strong causal evidence linking head impact to TBI and early CTE, independent of concussion,” said corresponding author Dr. Lee E. Goldstein, an associate professor at the School of Medicine and the College of Engineering. “The results may explain why approximately 20 percent of athletes with CTE never suffered a diagnosed concussion.”
“Our experimental results showed no correlation between concussive signs at the time of injury and CTE brain pathology. These findings provide strong evidence — the best evidence we have so far — that subconcussive impacts are not only dangerous but also causally linked to CTE,” Goldstein said.