Estrogen status affects sensitivity to focal cerebral ischemia in stroke-prone spontaneously hypertensive rats

Estrogen treatment has been shown to reduce ischemic brain damage. Because endogenous estrogen levels fluctuate markedly during the estrous cycle, we investigated the effect of stage of estrous cycle on ischemic brain damage. Halothane anesthetized 3- to Ei-mo-old female Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) in proestrus (high est radiol levels) or metestrus (low estradiol levels) underwent permanent midd le cerebral artery occlusion. In SHRSP, infarct volume at 24 h postocclusio n was 24% smaller in proestrus compared with metestrus [208.6 +/- 9.5 mm(3) (n = 7) vs. 272.7 +/- 23.8 mm(3) (n = 7), respectively, means +/- SE; P = 0.0278, unpaired t-test]. In WKY, infarct volumes were similar in proestrus and metestrus [157.0 +/- 5.4 mm(3) (n = 5) and 131.5 +/- 16.5 mm(3) (n = 8 ), respectively; P = not significant (NS)]. Brain swelling (ipsilateral min us contralateral hemispheric volumes) was similar in proestrus and metestru s for SHRSP [138 +/- 9 mm(3) (n = 6) and 136 +/- 10 mm(3) (n = 7), respecti vely] and for WKY [103 +/- 15 mm(3) (n = 5) and 90 +/- 11 mm(3) (n = 8), re spectively]. Thus the reduction in infarct size in SHRSP is caused by a tru e attenuation of the infarct volume and not simply by a reduction in brain edema.