SEX DIFFERENCES IN THE MICROGLIAL RESPONSES TO CEREBRAL ISCHEMIA
Monica M. Gaudier-Diaz, Ning Zhang, A. Courtney DeVries.
The Ohio State University, Columbus, OH.
Cerebral ischemia, caused by cardiac arrest and stroke, is a leading cause of death and disability worldwide. Thus, it is important to find ways to prevent it, facilitate recovery, and improve the quality of life of survivors. Social isolation increases neuroinflammation, neuronal death, and functional impairment following cerebral ischemia. We hypothesize that microglia, innate immune cells of the nervous system, modulate the detrimental effects of social isolation on ischemic outcome. Environmental stressors can sensitize microglia to respond in an exaggerated manner on further immune stimulation; it is plausible that social isolation does the same. To study the effects of social environment on the microglial response to cerebral ischemia, mice were pair-housed or socially isolated, and a week later exposed to cardiac arrest/cardiopulmonary resuscitation (CA/CPR) or the sham procedure. Brains were collected to measure microglial gene expression. Among individually housed male mice that received CA/CPR, there was increased microglial gene expression of proinflammatory cytokines IL-1β and IL-6 relative to sham controls; in contrast, gene expression among pair-housed males did not differ between CA/CPR and sham groups. This suggests that social isolation exacerbates ischemia-induced neuroinflammation through microglial production of proinflammatory cytokines. Nonetheless, in female mice there was increased microglial gene expression of proinflammatory cytokines following CA/CPR relative to sham regardless of housing. Additional studies are necessary to determine the mechanism underlying this sex difference on the effects of social environment on ischemia-induced neuroinflammation. In sum, social environment can have a substantial influence on the pathophysiological response to global cerebral ischemia.