Gender-linked brain injury in experimental stroke

Background and Purpose - Premenopausal women are at lower risk than men for stroke, but the comparative vulnerability to tissue injury once a cerebrovascular incident occurs is unknown. We hypothesized that female rats sustain less brain damage than males during experimental focal ischemia and that the gender difference in ischemic outcome can be eliminated by ovariectomy. Methods - Age-matched male (M), intact female (F), and ovariectomized female (O; plasma estradiol: 4.1±1.6 pg/mL compared with 7.4±1.5 in F and 4.0±1.1 in M) rats from two different strains, normotensive Wistar and stroke-prone spontaneously hypertensive rats, were subjected to 2 hours of intraluminal middle cerebral artery occlusion, followed by 22 hours of reperfusion. Cerebral blood flow (CBF) was monitored throughout the ischemic period by laser-Doppler flowmetry. Infarction volume in the cerebral cortex (Ctx) and caudoputamen (CP) was determined by 2,3,5- triphenyl-tetrazolium chloride staining. In a separate cohort of M, F, and O Wistar rats, absolute rates of regional CBF were measured at the end of the ischemic period by quantitative autoradiography using [¹⁴C]iodoantipyrine. Results - F rats of either strain had a smaller infarct size in Ctx and CP and a higher laser-Doppler flow during ischemia compared with respective M and O rats. Mean end-ischemic CBF was higher in F compared with M and O rats in CP, but not in Ctx. Cerebrocortical tissue volume with end-ischemic CBF <10 mL/100 g/min was smaller in F than M rats, but not different from O rats. Conclusions - We conclude that endogenous estrogen improves stroke outcome during vascular occlusion by exerting both neuroprotective and flow- preserving effects.