Sex is emerging as an important factor in the etiology and expression of many different pathological conditions, including stroke. Initially, the levels of sex hormones were thought to be the major contributor to these sex differences, especially after puberty, when gonadal steroid levels sharply diverge between the sexes. More recently, it is recognized that sex differences also result from the organizational effects of sex hormone exposure early in development, even in the absence of hormone exposure later in life, as well as effects mediated by the sex chromosomes themselves. Epigenetic modifications of developmental genes important in sexual differentiation and the response to sex steroid hormones are also emerging as another important contributor to sex differences in disease expression. This review describes recent research on the relationship between hormones, organizational-activational effects of gonadal steroids, and epigenetic modifications in brain pathology, focusing specifically on cerebral ischemia.
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