Phenotypic Changes in Immune Cell Subsets Reflect Increased Infarct Volume in Male vs. Female Mice

Inflammatory responses in the brain after cerebral ischemia have been studied extensively in male mice, but not female mice, thus potentially giving a less-than-accurate view of gender associated pathological processes. In humans, cerebral infarcts are typically smaller in premenopausal females than in age-matched males. In the current study, we confirmed smaller infarcts in female vs. male mice after middle cerebral artery occlusion and 96 h of reperfusion. Moreover, we explored immunological alterations related to this difference and found that the percentage of CD4⁺ T lymphocytes was significantly higher in spleens in males than females, with increased expression of the activation markers, CD69 and CD44. In contrast, the percentage of CD8⁺ T lymphocytes was significantly higher in spleens of females than males, leading to the identification of a small but distinct population of IL-10-secreting CD8⁺CD122⁺ suppressor T cells that were also increased in females. Finally, we observed that males have a greater percentage of activated macrophages/microglia in the brain than females, as well as increased expression of the VLA-4 adhesion molecule in both brain and spleen. This new information suggesting gender-dependent immunological mechanisms in stroke implies that effective treatments for human stroke may also be gender specific.