Repeated Mild TBI in Adolescent Rats Reveals Sex Differences in Acute and Chronic Behavioral Deficits.

High school students who participate in contact sports are vulnerable to sustaining multiple concussions and exhibit deficits in cognitive function in both the acute and chronic phases and in emotional behavior in the chronic phase. Further, boys are more likely to suffer cognitive problems whereas girls tend to report depression and anxiety. The effects of repetitive mild TBI in adolescent (35-40-day old) male and female Sprague-Dawley rats on object location and spatial working memory (hippocampal-dependent) and object recognition memory (hippocampal-independent) at 1-and-4-weeks post-injury along with trait-dependent anxiety- and depressive-like behaviors at 5 weeks were examined. Compared to sham-injured rats, male brain-injured rats demonstrated significant impairment in both hippocampal-dependent and -independent memory tasks at both time points, whereas female brain-injured rats only exhibited impairment in these tests at the 4-week time point. In contrast, depressive-like behaviors were present in the forced swim test in only the female brain-injured animals at 5 weeks post-injury; anxiety-like behaviors were not evident in either male or female brain-injured animals. Histological analysis at 6 weeks after injury revealed that repeated mild TBI in male and female adolescent rats resulted in increased reactivity of astrocytes and microglia within the corpus callosum below the impact site and in the stratum oriens and stratum pyramidale of the CA2 region of the dorsal hippocampus. Together, these data are indicative of the differences in the temporal pattern of post-traumatic behavioral deficits between male and female animals and that female animals may be more likely to develop deficits in the chronic post-traumatic period.