That since there was no stroke in group 1, there was little to no free radical production in the brain.In group 2, there was a strong induction of the free radical superoxide, produced by the enzyme, NADPH oxidase in the hippocampus following stroke.In Group 3, estrogen was found to strongly block the NADPH oxidase-induced production of superoxide, and it protected the brain and reduced oxidative damage to it. In group 4 animals, which had been deprived of estrogen for a prolonged period similar to the situation that occurs after menopause, the protective effect of estrogen on the brain was completely lost. It no longer blocked NADPH oxidase activation and superoxide production, and no longer protected the brain.In the long-term estrogen deprived animals, it was found that there was a significant loss in the hippocampus of one of the receptors for estrogen, thereby leading to the lost sensitivity to estrogen.In addition, another region of the hippocampus, the CA3 region, which is normally resistant to stroke damage, became hypersensitive to damage by stroke in the animals that had been deprived of estrogen for an extended period.

Thus, the study demonstrated that a long period of estrogen deprivation led to a loss of estrogen's sensitivity and protective effects in the hippocampus, and that some parts of the hippocampus that are normally resistant to stroke damage, lose this resistance when deprived of estrogen for a prolonged period of time.

ConclusionsAccording to Dr. Brann, "Every study has potential limitations, including ours. Our studies were performed in animals and it is unclear if the results are applicable to humans. Further research is needed to address this issue." Nevertheless, said Brann, "The study provides support for the idea that there is a "critical period" for beneficial effect of estrogen upon the brain and provides insights to the mechanisms underlying this critical period." He added, "It suggests studies in humans should focus on replacing estrogen prior to or at the time of menopause to examine for potential beneficial effects upon the brain."

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