Estrogens decrease reperfusion-associated cortical ischemic damage - An MRI analysis in a transient focal ischemia model

Background and Purpose-Early identification of irreversible cerebral ischem ia is critical in defining strategies that influence neuronal survival afte r stroke. We used MRI to investigate the effects of 17 beta -estradiol (E2) on the temporal evolution of focal ischemia. Methods-Female rats were ovariectomized and divided into 1 of 2 groups: ova riectomy alone (OVX; n=4) or ovariectomy with estrogen replacement (OVX+E2; n=3). Both groups were then subjected to I-hour middle cerebral artery occ lusion (MCAO), with the use of a standardized endovascular monofilament mod el, followed by reperfusion. Sequential diffusion-weighted (DWI) and T2-wei ghted (T2WI) MRI were obtained during and after the MCAO. In separate group s of animals (n=5 for OVX and OVX+E2), cerebral blood flow (CBF) was measur ed by laser-Doppler methods before, during, and after occlusion. Results-DWI detected similar lesion characteristics during MCAO in both gro ups. In the OVX group, lesion size did not change during reperfusion, but t he signal intensity ratio increased early and stabilized during the latter stages. In contrast, DWI lesion size decreased during reperfusion in OVX+E2 rats by 50% to 60% (P<0.05), a size reduction almost exclusively limited t o cortical regions. During MCAO, the signal intensity ratio in OVX+E2 rats was reduced compared with OVX rats. Reperfusion further attenuated the sign al intensity ratio in cortical but not subcortical regions (P<0.05 versus O VX). T2WI revealed no lesions in either group during MCAO, but it detected lesion sizes similar to that of DWI during reperfusion. Furthermore, simila r patterns and magnitudes of estrogen treatment-related decrease in lesion size were noted after reperfusion. T2WI demonstrated less intense signal in tensity ratio changes in both groups compared with DWI. There were no diffe rences in CBF between groups either during occlusion, early reperfusion, or 1 day after reperfusion. Conclusions-This study strongly suggests that estrogens selectively protect cortical tissue from ischemic damage during MCAO and that this protection is exerted during both the occlusion and reperfusion phases of ischemia and does not involve an estrogen-related change in CBF.