The new work originated at Boston University's Center for Chronic Traumatic Encephalopathy and drew in dozens of experts from a wide range of disciplines and institutions.
The team began by inspecting the brains of four teenage athletes who died one day, two days, 10 days and four months after suffering serious head injuries. Those brains were compared with others belonging to teen athletes who died without a history of head injury.
The researchers observed an abnormal buildup of a protein called tau -- a hallmark of CTE -- in two of the athletes who experienced head trauma. One, in fact, met the diagnostic criteria for early CTE.
That and other evidence led the researchers to hypothesize that early CTE may result from leaky blood vessels in the brain. In the deep recesses of the organ's folds, these damaged blood vessels were letting proteins spill into nearby brain tissue, triggering inflammation, they surmised.
To see whether they were right, they needed to study a population of subjects with greater rigor. So they built a machine to deliver calibrated blows to young male mice, subjecting them to a range of head impacts. The effects of these blows were recorded in imaging scanners, in test mazes and on pathology slides.
The researchers examined the animals' brain chemistry, cortical structure and behavior. Finally, they performed computer simulations to repeat and extend their findings on how various brain tissues responded to head impacts.
The results were all over the map. Delivered a powerful blow, some mice would reel from the injury for days but then recover. Upon dissection, their brains might even look fine.
Other mice, including many who got a series of blows equivalent to participating in a single game or practice, would behave normally in the days following a head impact. But not much later, their brains would reveal early signs of tau protein accumulations.
Sure enough, these deposits appeared to start in the deep recesses of the brain's folds, where the hallmarks of full-fledged CTE are most clearly seen in humans too.
The results may explain why approximately 20 percent of athletes who were found to have CTE after they died had never received a concussion diagnosis when they were alive, Goldstein said. And they suggest that people who seem to bounce right back after getting their "bell rung" may well have sustained damage that will not be evident for years.