Figure 2. Physiological levels of estradiol decrease ischemic brain damage following stroke injury. Representative coronal sections obtained from oil-treated (left) and estradiol-treated (right) rat brains collected 24 h after the onset of ischemia and stained … Estrogen protects against in vitro neural injury In addition to in vivo studies, several in vitro studies have greatly contributed to our understanding of estrogen action against degeneration. Many paradigms have been utilized to investigate whether estrogen Inhibitors,research,lifescience,medical can protect neural

cells, in vitro. Studies have been performed in primary neuronal cultures, mixed astrocyte/neuron cultures, cell lines, and Inhibitors,research,lifescience,medical organotypic cultures. Using these paradigms, investigators have aimed to reproduce the deleterious environments found in various neurodegenerative conditions such as AD and stroke and have then tested whether estrogen protects against cell death. In vitro studies clearly establish that estrogen exerts profound protective

effects against a variety of neurotoxic insults. Studies have induced injury through conditions that mimic AD toxicity,104-107 hypoxia, and oxidative stress,107-113 excitotoxicity,107,111,114-116 and physical injury.117 Thus, studies have examined whether estradiol can salvage cells from death induced by inhibition of mitochondrial function, suppression of glucose Inhibitors,research,lifescience,medical metabolism, alteration of nitric oxide production, or administration of substances such as β-amyloid peptide, excitatory amino acids, free radicals, Inhibitors,research,lifescience,medical and glycoprotein 120. Though the differing modes of injury are distinct, they may share similar mechanisms of toxicity and face final common pathways in the induction of cell death. It remains to be determined whether estradiol protects Inhibitors,research,lifescience,medical against cell death through parallel or divergent pathways in the different modes of injury. Estrogen does

not always protect It is important to appreciate that estrogen does not always exert beneficial effects. The actions of estrogen appear to be dictated by the type of estrogen administered, dose of estrogen given, and the animal model utilized. The type of estrogen administered impacts the efficacy of its neuroprotective actions. Most, studies have focused attention on the effects of 17β-cstradiol since it is the most, biologically active and potent endogenous estrogen. However, we have gained major Torin 2 insight into estrogen Ergoloid action through studies that have probed the effects of 17α-estradiol, an “inactive” stereoisomer that, does not effectively bind and activate ERs. The studies show that at physiological levels, 17β-estradiol protects and 17α-estradiol fails to protect against, brain injury,110 indicating that ERs arc critical to the mechanisms of hormone-mediated protection.12,118 However, the picture becomes more complex when we consider the dose of estrogen administered.