Assessment of Sex Differences Following Repeated Mild Head Injuries

There is limited information about sex differences in mRHI, despite some studies suggesting females participating in contact sports experience more head injuries than males. This study will test the hypothesis that mRHI will lead to more severe neurological deficits in female mice than in male mice. C57BL/6 female mice were assigned to sham and mRHI groups (n=30/group). Lightly anesthetized mice received 25 mild head injuries, once a day (M-F) over 5 weeks using a weight drop model that included a free fall with rotational injury. Acutely, mRHI female mice performed worse than sham injured mice on the balance beam (F (1,28) =4.309, P=0.0472) whereas there was no difference in males. 5 weeks and 15 weeks after injury mice underwent a 3-week series of behavioral tests. Both male and female mice in the mRHI groups performed significantly (T-test P< 0.01) worse on the Rotarod than uninjured controls. Only males in MWM showed significant impairment on memory for 5-week and significant impairment on spatial learning and memory for 15-week (Probe T-test P< 0.05). Only 15-week male mice showed deficits in elevated plus maze (EPM) (T-test P< 0.05). Acutely, female mice showed balance deficits that were not apparent in males. Fifteen weeks after mRHI, males no longer displayed deficits in the rotarod, but female mice continued to have a decrease in performance compared to controls (T-test, P<0.05). Unlike the males, female mice did not display any significant deficits in the MWM and EPM.