Their effects depend upon the concentration, whether they are given simultaneously or sequentially, the route of delivery, and on the age and health status of the women who receive hormone therapy. Turgeon et aP have provided a detailed review of our current understanding of estrogens, progestogens, their

related compounds, agonists, and Inhibitors,research,lifescience,medical antagonists. Estrogens and stroke Stroke is the third leading cause of death for middleaged and older women and a major health problem that affects 500 000 Americans each year.3 Every year approximately 40 000 more women than men are affected by stroke.4 Initially, this gender difference was thought to be explained by a combination of both the longer Inhibitors,research,lifescience,medical life expectancy of women and the protective roles of estrogen, since the incidence of stroke increases after menopause and the risk continues to rise with age.5 However, this interpretation has been questioned since recent clinical trials including the Women’s Health initiative (WHI) reported negative impact of estrogen therapy (ET)4,6-8 and some studies in animal models also suggest that estrogens are not universally protective and can be deleterious under some circumstances.9 In an attempt to reconcile these seemingly contradictory data, our lab has used animal Inhibitors,research,lifescience,medical models to explore the mechanisms of estrogen’s neuroprotective and neuroregenerative

actions. Estrogens and stroke: use of animal models to decipher mechanisms of action Even the best, well-designed Inhibitors,research,lifescience,medical clinical studies cannot benefit from the experimental advantages of many basic science studies, since studies performed with experimental animal models allow replication with adequate numbers of animals, controls with equivalent genetic backgrounds and

previous exposure to similar environments, Inhibitors,research,lifescience,medical wellcontrolled environments during the entire study, and lack of selection or recall bias. Thus, investigators have developed http://www.selleckchem.com/products/Temsirolimus.html several animal models to investigate the pathophysiology and potential treatments for stroke. Since most cerebrovascular strokes (>70%) in aging human populations are ischemic, and not hemorrhagic, we adopted an animal model that reproduces ischemic infarcts. We have utilized permanent middle cerebral artery Cilengitide occlusion (MCAO) as a model of permanent occlusion of the middle cerebral artery, which vascularizes the cerebral cortex, the striatum, and the hippocampus, to examine the effects of estrogen in neurodegeneration. Blockade of this artery at its base results in about a 50% decrease in blood flow and causes severe metabolic impairment in a core region, called the “ischemic core” and many neurons in these regions die by necrosis within hours following injury. In contrast, regions that surround the ischemic core, the ischemic penumbra, undergo more moderate metabolic impairment and are potentially salvageable by effective therapeutic agents.