STRAIN-RELATED DIFFERENCES IN SUSCEPTIBILITY TO TRANSIENT FOREBRAIN ISCHEMIA IN SV-129 AND C57BLACK 6 MICE/

Background and Purpose We explored susceptibility to injury after glob al ischemia in SV-129 and C57Black/6 mice, two commonly used backgroun d strains in genetically engineered mice. Methods Mice (n=84) were sub jected to 15, 30, or 75 minutes of bilateral common carotid artery (BC CA) occlusion followed by reperfusion for 72 hours. BCCA occlusion was performed under halothane or chloral hydrate anesthesia; in one exper iment, mean arterial blood pressure and regional cerebral blood flow ( laser Doppler flowmetry) were matched by controlled exsanguination. Ba seline absolute blood flow measurements were obtained in both strains using a tracer, N-isopropyl-[methyl 1,3-C-14]-p-iodoamphetamine, indic ator fractionation technique (n = 5 per group). Vascular anatomy of th e circle of Willis was visualized by intravascular perfusion of carbon black ink (n = 10 per group). Cerebrovascular reactivity was assessed by measuring the diameter of pial vessels (intravital microscopy) to acetylcholine (ACh) superfusion (0.1 to 10 mmol/L) in a closed cranial window preparation (n = 29). Results Resting blood flow values did no t differ between groups in striatum, cerebellum, and brain-stem region s. SV-129 mice were less susceptible than C57Black/6 mice to ischemic injury (0.0+/-0.0 versus 1.3+/-0.3 damage in hippocampal CA1 region af ter 30 minutes of ischemia in SV-129 and C57Black/6, respectively; P<. 01). Cellular damage (grade 1 to 3 injury) comparable to 30-minute BCC A occlusion was achieved only after 75 minutes of ischemia in SV-129 m ice (1.1+/-0.3). Ischemic damage was also significantly less in SV-129 mice after blood pressure and flow were matched during ischemia in ha lothane anesthetized SV-129 mice (0.5+/-0.3 versus 1.4+/-0.2, P<.05), or after chloral hydrate anesthesia (0.4+/-0.2 versus 1.5+/-0.4, P<.05 ). Hypoplastic posterior communicating arteries were found in all 10 C 57Black/6 mice and may explain the greater susceptibility of these mic e to injury after BCCA occlusion. More robust vasodilation to ACh in C 57Black/6 mice could also indicate genetic differences in responses to vasoactive substances. Conclusions C57Black/6 mice exhibit enhanced s usceptibility to global cerebral ischemic injury, an incompletely form ed circle of Willis, and augmented pial vessel dilation to ACh compare d with SV-129 mice. Our findings suggest that strain differences may c onfound results when genetically engineered mice generated from more t han a single background strain are used.