Sex differences in the inflammatory response to stroke

Ischemic stroke is a leading cause of morbidity and mortality and disproportionally affects women, in part due to their higher longevity. Older women have poorer outcomes after stroke with high rates of cognitive deficits, depression, and reduced quality of life. Post-stroke inflammatory responses are also sexually dimorphic and drive differences in infarct size and recovery. Factors that influence sex-specific immune responses can be both intrinsic and extrinsic. Differences in gonadal hormone exposure, sex chromosome compliment, and environmental/social factors can drive changes in transcriptional and metabolic profiles. In addition, how these variables interact, changes across the lifespan. After the onset of ischemic injury, necrosis and apoptosis occur, which activate microglia and other glial cells within the central nervous system, promoting the release of cytokines and chemokines and neuroinflammation. Cells involved in innate and adaptive immune responses also have dual functions after stroke as they can enhance inflammation acutely, but also contribute to suppression of the inflammatory cascade and later repair. In this review, we provide an overview of the current literature on sex-specific inflammatory responses to ischemic stroke. Understanding these differences is critical to identifying therapeutic options for both men and women.