Evaluation of estrous cycle stage and gender on behavioral outcome after experimental traumatic brain injury

Female sex hormones are acutely neuroprotective in experimental models of traumatic brain injury (TBI). Because hormonal profiles are known to vary with estrous cycle stage, the purpose of this study was to evaluate how pre-injury estrous stage affects motor and cognitive performance after experimental TBI. We also sought to compare post-injury behavioral performance in males vs. females. Under anesthesia, male (n=18) and female (n=35) Sprague-Dawley rats underwent either controlled cortical impact (CCI) injury (2.7 mm; 4 m/s) or sham operations. Females were grouped according to estrous stage (proestrous or non-proestrous) at the time of surgery. Motor function was assessed pre-injury and for the first 5 days after surgery using beam balance and walking tasks. Spatial memory was assessed beginning 14 days post-injury utilizing the Morris water maze (MWM) task. No significant differences were found on any task between injured females regardless of estrous cycle stage. Females performed significantly better than males on both motor tasks, but gender did not influence MWM performance. Mixed effects multivariate analysis corroborated these results by showing that pre-injury serum hormone levels had little affect on behavioral performance. The results suggest that the presence of endogenous circulating hormones, rather than hormonal status at time of injury, may confer early neuroprotection in females after TBI. The impact of early neuroprotection on later behavioral outcome and the anatomic structural specificity of hormonal neuroprotection require further study.