Estradiol exerts neuroprotective actions against ischemic brain injury: Insights derived from animal models

Over the last 100 yr, the life-span of women has increased from 50 yr to over 80 yr, but the age of the menopause has remained unchanged, at 51 yr. Menopause is one of the most permanent physiologic changes that a woman will experience and is marked by a dramatic decrease in circulating levels of ovarian estrogens. Because the timing of menopause has remained fixed in the face of an increasing life-span, more women will live a greater proportion of their lives in a hypoestrogenic state. We appreciate more and more that the actions of ovarian steroid hormones are complex, and possibly exert opposing actions in different contexts. I review here the results of my laboratory's recent studies that clearly establish that low physiologic levels of estradiol replacement can exert profound neuroprotective actions when administered prior to an ischemic strokelike injury.