Susceptibility to Cerebral Infarction in the Stroke-Prone Spontaneously Hypertensive Rat Is Inherited as a Dominant Trait

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Abstract
Background and Purpose —Susceptibility to cerebral infarction was compared in stroke-prone spontaneously hypertensive (SHRSP), normotensive Wistar-Kyoto (WKY) rats, and F 1 hybrids derived from a SHRSP/WKY cross. Methods —The proximal left middle cerebral artery (MCA) was occluded under anesthesia and infarct volume assessed 24 hours later by magnetic resonance imaging and confirmed 5 days later by quantitative histopathology. Total hemispheric infarct volume was expressed as a percentage of the total brain volume. Results —Infarct volumes measured by MRI in adult SHRSP (19.5±2.0%) and F 1 hybrid rats (19.4±1.9%) were significantly greater than in WKY (11.1±2.4; CI [6.07, 10.76]) and (5.93, 10.52), respectively, P <.001). Sensitivity to an ischemic insult was unrelated to blood pressure: although systolic blood pressures differed between young versus adult male SHRSP and between female versus male SHRSP and F 1 hybrids, infarct volumes were equal. A close correlation was found between infarct volumes measured by MRI and histology ( r =.92, P <.0001). Conclusions —Outcome to MCA occlusion (MCAO) measured with MRI provides a reproducible and nonterminal quantitative phenotypic marker of stroke susceptibility in the SHRSP. This is the first study to employ MCAO with MRI to quantify stroke susceptibility in F 1 hybrid rats and indicates a dominant mode of inheritance for this phenotype.