Inducible nitric oxide synthase and estradiol exhibit complementary neuroprotective roles after ischemic brain injury.

Estradiol-17beta exerts profound neuroprotective actions following cerebral ischemia through multiple molecular mechanisms. To examine the putative anti-inflammatory mechanisms employed by estradiol during stroke, we explored the interactions between estradiol and inducible nitric oxide synthase (iNOS) in both wildtype and iNOS knockout (iNOSKO) female mice following permanent middle cerebral artery occlusion (MCAO). Female mice were ovariectomized and treated with estradiol.

Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions.

Recent studies describing the seemingly contradictory actions of estrogens in ischemic stroke injury have led us to reevaluate the circumstances under which estrogen therapy (ET) provides benefits against cerebral stroke and decipher its mechanisms of action. One prominent feature that follows stroke injury is massive central and peripheral inflammatory responses. Evidence now suggests that postischemic inflammatory responses strongly contribute to the extent of brain injury, and 17beta-estradiol (E(2)) may protect the ischemic brain by exerting antiinflammatory actions.