Abstract #9: Gender Related Outcome Differences after Experimental Mild Traumatic Brain Injury

Mild traumatic brain injury (mTBI) has been less well studied than moderate or severe injuries. Emerging clinical evidence from sports related mTBI suggests that females may have worse outcomes than males, yet few animal studies have addressed this issue. The present study compared neurobehavioral and neuropathological outcomes after experimental mTBI in male versus female mice subjected to controlled cortical impact (CCI) brain injury. Male and female C57BL/6 mice (20–25 g) were subjected to mild CCI (each n = 13) or sham injury (each n = 7). Fine motor co-ordination was evaluated by a beam walk (BW) test at 1 day, 3 days, 7 days, 14 days, and 21 days after injury and cognitive function was assessed using the Morris water maze (MWM) at 15–18 days after injury. T2-weighted MRI was performed on all mice at 21 days after mild CCI, and the injury-mediated lesion volume in each mouse brain was calculated. Mild CCI caused only a slight increase in the number of foot faults in BW in both male and female mice, without significant gender differences. In the MWM, injured male mice did not show impairments in learning and memory, compared with shams. In contrast, in female mice the latency to locate a submerged platform was significantly increased when compared with either sham or male animals ( p < 0.05). In addition, MRI showed significantly larger lesion volumes in female mice compared with males at 21 days ( p < 0.05). In contrast to long-held views that females may be somewhat protected from brain trauma by virtue of estrogen or progesterone, recent clinical evidence in mTBI suggests otherwise. The current study supports these clinical observations and demonstrates that cognitive impairments are found in female but not male mice following mTBI, with parallel larger lesion volumes. This model may be used to address potential mechanisms that may account for these gender differences.