Chronic 17beta-estradiol pretreatment and ischemia-induced hippocampal degeneration and memory impairments: a 6-month survival study.

Exogenous administration of estrogen has been shown to significantly reduce ischemia-induced neuronal degeneration. However, the long-term impact of such treatment on neuronal protection and functional recovery remain largely unknown. The present study assessed the effects of a 15-day pretreatment with 17beta-estradiol on memory deficits and neuronal damage up to 6 months following a 10-min global ischemia in rats. Four groups of ovariectomized female rats [sham-operated and ischemic rats receiving a 15-day pretreatment of either the vehicle or 17beta-estradiol (100 microg/kg)] were tested. The 8-arm radial maze and object recognition tests served to evaluate the impact of 17beta-estradiol treatment on ischemia-induced spatial and recognition memory impairments, respectively. Testing in the radial maze was initiated at two distinct time intervals following reperfusion (7 and 120 days) to evaluate changes in memory functions over time. Our findings revealed long-lasting neuroprotective effects of 17beta-estradiol treatment on hippocampal CA1 pyramidal cells in ovariectomized ischemic rats (43.5% greater neuronal survival than observed in vehicle-treated ischemic animals). Importantly, this neuronal protection translated into significant improvements of recognition and spatial memory functions in estradiol-treated ischemic rats.