ESTRADIOL PROTECTS AGAINST ISCHEMIC-INJURY

Clinical studies demonstrate that estrogen replacement therapy in post menopausal women may enhance cognitive function and reduce neurodegene ration associated with Alzheimer's disease and stroke. This study asse sses whether physiologic levels of estradiol prevent brain injury in a n in vivo model of permanent focal ischemia. Sprague-Dawley rats were ovariectomized; they then were implanted, immediately or at the onset of ischemia, with capsules that produced physiologically low or physio logically high 17 beta-estradiol levels in serum (10 or 60 pg/mL, resp ectively). One week after ovariectomy, ischemia was induced. Estradiol pretreatment significantly reduced overall infarct volume compared wi th oil-pretreated controls (mean +/- SD: oil = 241 +/- 88; low = 139 /- 91; high = 132 +/- 88 mm(3)); this protective effect was regionally specific to the cortex, since no protection was observed in the stria tum. Baseline and ischemic regional CBF did not differ between oil and estradiol pretreated rats, as measured by laser Doppler flowmetry. Ac ute estradiol treatment did not protect against ischemic injury, Our f inding that estradiol pretreatment reduces injury demonstrates that ph ysiologic levels of estradiol can protect against neurodegeneration.