FRIDAY, Nov. 6 (HealthDay News) -- Estrogen can protect the brain against stroke damage by free radicals, but only if present before the stroke, which may shed light on why women are more susceptible to stroke damage after menopause, according to a study in the Nov. 4 issue of the Journal of Neuroscience.

Noting that estrogen (E₂, 17β-estradiol) is known to have a neuroprotective effect, but that a clinical trial did not find that estrogen was protective in menopausal women, Quan-Guang Zhang, Ph.D., from the Medical College of Georgia in Augusta, and colleagues induced a stroke in ovariectomized rats, treating them with estrogen before or after the stroke.

The researchers found that stroke was associated with an NADPH oxidase-induced increase in the free radical superoxide in CA1 neurons of the hippocampus, which was strongly reduced in rats treated with estrogen before the stroke. However, there was no protective effect in rats deprived of estrogen before the stroke, which was associated with a loss of estrogen receptor-α in the hippocampus. In addition, the CA3/CA4 region of the hippocampus became hypersensitive to stroke damage in animals deprived of estrogen before the stroke.

"In conclusion, the current study advances the field by elucidating a novel and potent extranuclear estrogen receptor-α-mediated action of E₂ in the brain to suppress NADPH oxidase activation and superoxide generation in hippocampal CA1 neurons after stroke," Zhang and colleagues write. "Finally, it demonstrates that the often ignored CA3/CA4 becomes hypersensitive to injury after long-term E₂ deprivation, which may help explain the increased risk of cognitive decline and dementia observed after prolonged hypoestrogenicity or long-term ovariectomy in women."

Abstract
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