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(Stroke. 1997;28:1805-1811.)
© 1997 American Heart Association, Inc.
Articles |
Strain-Related Differences in Susceptibility to Transient Forebrain Ischemia in SV-129 and C57Black/6 Mice
From the Stroke and Neurovascular Regulation Laboratory, Department of Neurosurgery and Neurology (M.F., H.H., W.M., Z.H., M.A.M.), and the Neuropathology Service (J.P.V.), Massachusetts General Hospital, Harvard Medical School, Boston, Mass.
Correspondence to Michael A. Moskowitz, MD, Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, Harvard Medical School, CNY 6403, 149 13th St, Charlestown, MA 02129. Email moskowitz{at}helix.mgh.harvard.edu
Background and Purpose We explored susceptibility to injury after global ischemia in SV-129 and C57Black/6 mice, two commonly used background strains in genetically engineered mice.
Methods Mice (n=84) were subjected to 15, 30, or 75 minutes of bilateral common carotid artery (BCCA) occlusion followed by reperfusion for 72 hours. BCCA occlusion was performed under halothane or chloral hydrate anesthesia; in one experiment, mean arterial blood pressure and regional cerebral blood flow (laser Doppler flowmetry) were matched by controlled exsanguination. Baseline absolute blood flow measurements were obtained in both strains using a tracer, N-isopropyl-[methyl 1,3-14C]-p-iodoamphetamine, indicator fractionation technique (n=5 per group). Vascular anatomy of the 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 not differ between groups in striatum, cerebellum, and brain-stem regions. 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 after 30 minutes of ischemia in SV-129 and C57Black/6, respectively; P<.01). Cellular damage (grade 1 to 3 injury) comparable to 30-minute BCCA occlusion was achieved only after 75 minutes of ischemia in SV-129 mice (1.1±0.3). Ischemic damage was also significantly less in SV-129 mice after blood pressure and flow were matched during ischemia in halothane-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 C57Black/6 mice and may explain the greater susceptibility of these mice to injury after BCCA occlusion. More robust vasodilation to ACh in C57Black/6 mice could also indicate genetic differences in responses to vasoactive substances.
Conclusions C57Black/6 mice exhibit enhanced susceptibility to global cerebral ischemic injury, an incompletely formed circle of Willis, and augmented pial vessel dilation to ACh compared with SV-129 mice. Our findings suggest that strain differences may confound results when genetically engineered mice generated from more than a single background strain are used.
Key Words: cerebral ischemia, transient • mice • genetic engineering • circle of Willis
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