Biologic sex is an important genetic factor in the incidence and outcome of cerebral ischemia and clinical stroke. Emerging experimental data suggest that gender and background reproductive steroids shape ischemic cell death in the brain. The principal mammalian estrogen (17P-estradiol) is neuroprotective in many types of brain injury, whereas androgens appear to exacerbate ischemic damage. These hormones clearly contribute to, but do not fully account for, sex-specific responses to cerebral ischemia. The purpose of this chapter is (i) to review the importance of biologic sex to clinical and experimental stroke outcome and injury mechanisms, (ii) to summarize the controversy behind estradiol's neuroprotective properties, and (iii) to introduce the novel concept that androgens contribute to ischemic sensitivity in the male brain.

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