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 femal
e rats sustain less brain damage than males during experimental focal
ischemia and that the gender difference in ischemic outcome can be eli
minated by ovariectomy, Methods-Age-matched male (M), intact female (F
), and ovariectomized female (O; plasma estradiol: 4.1 +/- 1.6 pg/mL c
ompared with 7.4 +/- 1.5 in F and 4.0 +/- 1.1 in M) rats from two diff
erent strains, normotensive Wistar and stroke-prone spontaneously hype
rtensive rats, were subjected to 2 hours of intraluminal middle cerebr
al artery occlusion, followed by 22 hours of reperfusion. Cerebral blo
od flow (CBF) was monitored throughout the ischemic period by laser-Do
ppler flowmetry. Infarction volume in the cerebral cortex (Cts) and ca
udoputamen (CP) was determined by 2,3,5-triphenyl-tetrazolium chloride
staining. In a separate cohort of M, F, and O Wistar rats, absolute r
ates of regional CBF were measured at the end of the ischemic period b
y quantitative autoradiography using [C-14]iodoantipyrine. Results-F r
ats of either strain had a smaller infarct size in Ctx and CP and a hi
gher 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 r
ats in CP, but not in Ctx. Cerebrocortical tissue volume with end-isch
emic CBF <10 mL/100 g/min was smaller in F than M rats, but nor differ
ent from O rats. Conclusions-We conclude that endogenous estrogen impr
oves stroke outcome during vascular occlusion by exerting both neuropr
otective and flow-preserving effects.