Gender-Linked Brain Injury in Experimental Stroke

TLDR

Premenopausal women have a lower stroke risk than men, but how gender influences brain injury after a stroke remains unclear. The study tested whether female rats sustain less brain damage than males in experimental focal ischemia and whether ovariectomy eliminates this gender difference. Male, intact female, and ovariectomized female rats from Wistar and stroke‑prone hypertensive strains underwent 2‑hour middle cerebral artery occlusion followed by 22‑hour reperfusion, with cerebral blood flow monitored by laser‑Doppler and infarct volume measured by TTC staining, and a separate cohort had regional CBF quantified by autoradiography. Female rats exhibited smaller cortical and caudoputamen infarcts and higher ischemic CBF, especially in the caudoputamen, indicating that endogenous estrogen confers neuroprotection and preserves cerebral perfusion during stroke.

Abstract

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-triphenyltetrazolium 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 [ 14 C]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.