Sex-Specific Immune Responses in Stroke

Abstract

In both acute and chronic diseases, functional differences in host immune responses arise from a multitude of intrinsic and extrinsic factors. Two of the most important factors affecting the immune response are biological sex and aging. Ischemic stroke is a debilitating disease that predominately affects older individuals. Epidemiological studies have shown that older women have poorer functional outcomes compared with men, in part due to the older age at which they experience their first stroke and the increased comorbidities seen with aging. The immune response also differs in men and women, which could lead to altered inflammatory events that contribute to sex differences in poststroke recovery. Intrinsic factors including host genetics and chromosomal sex play a crucial role both in shaping the host immune system and in the neuroimmune response to brain injury. Ischemic stroke leads to altered intracellular communication between astrocytes, neurons, and resident immune cells in the central nervous system. Increased production of cytokines and chemokines orchestrate the infiltration of peripheral immune cells and promote neuroinflammation. To maintain immunosurveillance, the host immune and central nervous system are highly regulated by a diverse population of immune cells which are strategically distributed within the neurovascular unit and become activated with injury. In this review, we provide a comprehensive overview of sex-specific host immune responses in ischemic stroke.