Sex differences in neuropathological response to traumatic brain injury: increased neuronal loss and astrogliosis in females.

Traumatic brain injury (TBI) is one of the most common causes of disability worldwide and a risk factor for the development of post-traumatic epilepsy and mood disorders. Sexual differences in the tissue response to the injury may contribute to the varied pathophysiology of TBI, making it particularly challenging to develop a satisfactory therapy. The aim of this study was to investigate the sexual difference in astrogliosis, microgliosis, and neuronal loss after TBI. Penetrating cortical brain injury was performed in male and female rats that were sacrificed 2, 8, 16, or 30 days after injury. Glial scar development and neuronal loss were analysed, as well as the morphology of astrocytes and microglia in perilesional cerebral cortex. Increased astrogliosis was observed in females compared to males, including more complex and hypertrophied morphology of astrocytes 2 and 8 days after TBI, an earlier onset of contralateral astrocytic reaction, and a greater GFAP + (glial fibrillary acidic protein) area fraction in perilesional cortex in females 30 days post-injury. Sex differences in microglia morphology were also observed, such as more complex and ramified microglia in females 2 and 30 days after TBI. Moreover, an increased loss of parvalbumin- and neuropeptide Y-expressing neurons in perilesional and contralateral cortex was noticed in females compared to males, along with a higher number of cells expressing neuronal nitric oxide synthase. These results suggest a sexual differences in the cellular response to traumatic brain injury, which may contribute to the different outcomes and development of post-traumatic pathologies in males and females.