Deleterious effect of beta-estradiol in a rat model of transient forebrainischemia

Estrogen has demonstrated great potential as a therapeutic agent in focal i schemic brain injury. as exogenous P-estradiol has proven beneficial in a v ariety of focal stroke models. In contrast. the relatively few studies of e strogen's efficacy in transient forebrain ischemia have produced inconsiste nt results. The present study was therefore designed To clarify estrogen's neuroprotective potential in selective hippocampal neuronal injury resultin g from four-vessel occlusion in the rat. Female Wistar rats (normal, ovarie ctomized, or ovariectomized and estradiol-treated) received 5 or 10 min of ischemia. No differences in hippocampal cell loss were found amongst the gr oups with 10 min of ischemia. Amongst the groups with 5 min of ischemia, th e mildest injury was found in the ovariectomized animals, which lost only 3 2% of their CA1 pyramidal cells. In comparison, mean cell losses were 54% a nd 49%, respectively, in intact females and in ovariectomized animals with estradiol replacement. Linear regression analysis demonstrated a highly sig nificant relationship between cell loss and plasma estradiol levels. The me chanism by which exogenous and endogenous estrogen exacerbated the injury i s unclear, as estrogen has many neuroprotective effects. On the other hand, many other reported effects of estrogen in hippocampal area CA1 might conf er increased sensitivity to ischemia, either by modulating the excitatory e ffects of glutamate or by modifying the inhibitory effects of GABA. Determi ning how to modulate the various competing effects of estrogen is of both t heoretical and practical importance. as it is now clear that one cannot ass ume that estrogen administration will always improve outcome in cerebral is chemia. (C) 2001 Elsevier Science B.V. All rights reserved.