Estrogen provides neuroprotection in transient forebrain ischemia through perfusion-independent mechanisms in rats

Background and Purpose-Estrogen-related neuroprotection in association with animal models of transient forebrain and focal ischemia has been documente d in several recent reports, Some of those studies indicated that part of t hat benefit was a function of improved intraischemic vasodilating capacity. In the present study we examined whether chronic estrogen depletion and re pletion affected ischemic neuropathology through perfusion-independent mech anisms. Methods-Normal, ovariectomized (OVX), and OVX female rats treated with 17 b eta-estradiol (E-2) were subjected to 30 minutes of transient forebrain isc hemia (right common carotid occlusion plus hemorrhagic hypotension) and rep erfusion. Neurological function and brain histopathology were assessed over the 72-hour recovery period. In all rats, preischemic and intraischemic co rtical cerebral blood flow (CBF) levels were monitored with laser-Doppler f lowmetry. In additional rats, CBF changes in the striatum and hippocampus w ere also monitored with laser-Doppler flowmetry probes and radiolabeled mic rospheres. In each experiment, the level of ischemia was targeted to a 75% to 80% reduction in cortical CBF. Results-The similarity in ischemic severity among groups was supported by m easurements of comparable patterns of electroencephalographic power changes during the ischemic period. Compared with normal females, OVX rats showed diminished neurological outcomes and more severe histopathology in the hipp ocampus and striatum. Two-week treatment of OVX rats with E-2 was accompani ed by postischemic neuropathological changes similar to those seen in norma l females. Intraischemic CBF reductions in the hippocampus and striatum wer e similar in all groups (to 35% to 50% of the preischemic value) but signif icantly less than the cortical CBF reductions. Conclusions-These findings indicate that estrogen provides ischemic neuropr otection through mechanisms unrelated to improvement of intraischemic cereb ral perfusion.