Estradiol protects against ischemic brain injury in middle-aged rats

Several clinical studies suggest that estradiol acts as a potent growth and protective factor in the adult brain. Postmenopausal women experience perm anent hypoestrogenicity and suffer from increased risk of brain injury asso ciated with neurodegenerative diseases such as stroke and Alzheimer's disea se, Estrogen replacement therapy appears to decrease the risk and severity of these neurodegenerative conditions. Studies using animal models have sho wn that estradiol exerts similar effects in rodents and can enhance cell su rvival and induce synaptic plasticity, Therefore, we undertook studies to a ssess whether estradiol treatment can decrease brain injury and cell death induced by an experimental model of ischemia and whether aging animals rema in responsive to the protective effects of estradiol. We will review result s from recent studies that demonstrate that 1) in young animals, estrogens exert profound protective effects against ischemic brain injury induced by cerebral artery occlusion and 2) the response of aging animals has been tes ted with varying results, We will discuss and compare our experimental find ings that utilize a permanent cerebral artery occlusion model and physiolog ical levels of estradiol replacement therapy in young and middle-aged rats with those of previous studies. These observations provide important insigh ts into the potential protective actions of estrogen replacement therapy on age- and disease-related processes in the brain.