Genetic and Gender Influences on Sensitivity to Focal Cerebral Ischemia in the Stroke-Prone Spontaneously Hypertensive Rat

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Abstract
—We have investigated genetic transmission of increased sensitivity to focal cerebral ischemia and the influence of gender in the stroke-prone spontaneously hypertensive rat (SHRSP). Halothane-anesthetized, 3- to 5-month-old male and female Wistar-Kyoto rats (WKY), SHRSP, and the first filial generation rats (F 1 crosses 1 and 2) underwent distal (2 mm) permanent middle cerebral artery occlusion (MCAO) by electrocoagulation. Infarct volume was measured by using hematoxylin-eosin–stained sections and image analysis 24 hours after ischemia and expressed as a percentage of the volume of the ipsilateral hemisphere. Infarct volume in males and females grouped together were significantly larger in SHRSP, F 1 cross 1 (SHRSP father), and F 1 cross 2 (WKY father), at 36.6±2.3% (mean±SEM, P P P 1 cross 1 (18.9±2.4%, n=6) developed significantly smaller infarcts than male F 1 cross 2 (32.8±2%, n=8, P 1 cross 1 and cross 2 hybrids, suggesting a dominant or codominant trait; response to cerebral ischemia appears to be affected by gender and stage in the estrous cycle. In addition, the male progenitor of the cross (ie, SHRSP versus WKY) influences stroke sensitivity in male F 1 cohorts.