Sex Differences in Postischemic Neuronal Necrosis in Gerbils

Abstract

Twenty-four hour postischemic neuronal necrosis was compared in male vs. female Mongolian gerbils subjected to a 3-h period of severe incomplete hemispheric ischemia produced by unilateral carotid occlusion. The incidence of stroke-prone males was 42.9% versus 26.7% for the females. Among the stroke-prone animals, the males displayed significantly greater neuronal necrosis at 24 h after ischemia compared to the females in the cerebral cortex and CA, region of the hippocampus. In the CA, region of the stroke-prone males, only 2.0% of the normal neuronal population remained by 24 h compared to 36.8% in the stroke-prone females (p < 0.02). In the cerebral cortex, the males had only 19.9% of normal versus 58.2% in the females (p < 0.05). In a second series of mechanistic experiments, no differences in cortical blood flow (CBF) were disclosed between preselected male and female stroke-prone animals before, during, or for 2 h after ischemia. As with the CBF, the extent of cortical extracellular hypocalcia during ischemia did not differ significantly. However, the degree of postischemic recovery of cortical extracellular calcium was significantly better in the females from 30 min to 2 h after reperfusion. In the same experiments, hemispheric vitamin E levels were measured at the 2 h time point as an index of postischemic brain lipid peroxidation. No difference in baseline vitamin E levels was observed between male and female sham-operated gerbils. In the males subjected to 3 h of ischemia plus 2 h of reperfusion, the hemispheric vitamin E decreased by 43.5% compared to the sham-operated males. In contrast, the females displayed only a 4.2% decline (p < 0.05 versus males). Previous studies showing the protective efficacy of antioxidants in this model have suggested an important role of oxygen radical-induced lipid peroxidation. Thus, it is proposed that the lesser ischemic vulnerability of females may be based upon an antioxidant effect of endogenous estrogen. Indeed, estrogen was found to be a more potent inhibitor of iron-catalyzed lipid peroxidation in brain tissue than vitamin E.