Repeated concussions in youth cause sex-specific changes

Youth are more susceptible to concussion—also known as mild traumatic brain injury (mTBI)—than adults. As childhood represents a period of significant brain development, there is concern that youth who sustain multiple concussions could suffer from long-term neurological consequences.

In a recent paper published in the Journal of Neuroinflammation, first author Katie Neale (pictured; Christie Lab) and fellow lab members investigated the acute effects of repeated mTBI (r-mTBI) on neurological function and cellular proliferation in both male and female juveniles. Surprisingly, they found that neurological deficits did not increase in severity with repeated injuries. They did find, however, that r-mTBI led to sex-specific cellular changes.

R-mTBI increased cellular production in the dentate gyrus, a part of the hippocampus thought to be responsible for the formation of episodic memory as well as the exploration of new environments, particularly in male models. This increase only occurred briefly, though, with rates eventually returning to normal. Using triple labeling experiments, Neale and her fellow researchers revealed that a high proportion of the proliferating cells were microglia/macrophages. This suggests that the increase in cellular production is a neuroinflammatory response, and the authors found that this response is focused around the mid-brain rather than peripheral cortical regions.

These results suggest that therapies targeting cellular proliferation could help reduce the short-term consequences of repeated concussions in youth, but there may be sex-specific considerations. They also add to the growing literature indicating sex differences in proliferative and inflammatory responses following r-mTBI.