Genetic and gender influences on sensitivity to focal cerebral ischemia inthe stroke-prone spontaneously hypertensive rat

We have investigated genetic transmission of increased sensitivity to focal cerebral ischemia and the influence of gender in the stroke-prone spontane ously hypertensive rat (SHRSP). Halothane-anesthetized, 3- to 5-month-old m ale and female Wistar-Kyoto rats (WKY), SHRSP, and the first filial generat ion rats (F-1 crosses 1 and 2) underwent distal (2 mm) permanent middle cer ebral artery occlusion (MCAO) by electrocoagulation. Infarct volume was mea sured by using hematoxylin-eosin-stained sections and image analysis 24 hou rs after ischemia and expressed as a percentage of the volume of the ipsila teral 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 +/- 22.3% (mean +/- SEM, P < 0.001, n = 15), 25.4 +/ - 2.4% (P < 0.01, n = 14), and 33.9 +/- 1.6% (P < 0.001, n = 18), respectiv ely, compared with WKY (14 +/- 2%, n = 17). Male F-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 < 0.005). Females, which underwent ischemia during mete strus, developed larger infarcts than respective males. A group of females in which the cycle was not controlled for developed significantly smaller i nfarcts than females in metestrus. Thus, the increased sensitivity to MCAO in SHRSP is retained in both F-1 cross 1 and cross 2 hybrids, suggesting a dominant or codominant trait; response to cerebral ischemia appears to be a ffected by gender and stage in the estrous cycle. In addition, the male pro genitor of the cross (ie, SHRSP versus WKY) influences stroke sensitivity i n male F-1 cohorts.