Sexual dimorphism in cerebral ischemia injury

Stroke is a leading cause of permanent disability and death. A complex series of biochemical and molecular mechanisms (e.g. the release of ROS/NOS, proapoptotic proteins and proinflammatory cytokine; neuronal depolarization, Ca2+ accumulation and so on) impair the neurologic functions of cerebral ischemia and stroke. We have known for some time that the epidemiology of human stroke is sexually dimorphic until late in life, well beyond the years of reproductive senescence and menopause. The principal mammalian estrogen (17β estradiol or E2) is neuroprotective in many types of brain injury and has been the major focus of investigation over the past several decades. However the incidence of stroke in women is lower than in men until decades past menopause, suggesting that factors beyond sex hormone contribute to these epidemiological sex differences. So a new concept is emerging: both sex steroids and biologic sex are important factors in clinical and experimental strokes. In this review, we will address sex steroids and gender differences in influencing the mechanisms and outcomes of brain ischemia stroke. These sex differences need to be identified which could help future translation to human neuroprotection.