Differences in Vulnerability to Permanent Focal Cerebral Ischemia Among 3 Common Mouse Strains

Abstract

Background and Purpose-Genetically engineered mice are used to study the role of single genes in cerebral ischemia, but inherent, strain-dependent differences in neuronal vulnerability may affect experimental end points. To examine this possibility, tissue injury resulting from focal ischemia and its relationship to cerebral hemodynamics were determined in 3 common mutant mouse strains. Methods-Permanent middle cerebral artery ligation was performed in male C57BL/6J, Balb/C, and 129X1/SvJ mice.Mean arterial blood pressure, blood gases, basal and postischemic cortical blood flow ([ 14 C]iodoantipyrine autoradiography and laser-Doppler flowmetry), posterior communicating artery patency, and infarct size were determined. Results-Basal cortical blood flow did not differ among strains. Ten minutes after middle cerebral artery ligation, relative red cell flow in the ischemic cortex was 6% to 7% of preischemic flow in every strain. Despite similar hemodynamics, cortical infarcts in Balb/C mice were 3-fold larger than those in 129X1/SvJ and C57BL/6J mice; infarct size in the latter 2 strains was not significantly different. The posterior communicating artery was either poorly developed or absent in Ͼ90% of the Balb/C and C57BL/6J but in Ͻ50% of the 129X1/SvJ mice. Conclusions-The extent of ischemic injury differed markedly between the 3 strains. The presence and patency of posterior communicating arteries, although variable among strains, did not affect preischemic or postischemic cortical blood flow or bear any relationship to ischemic injury. Therefore, intrinsic factors, other than hemodynamic variability, may contribute to the differences in ischemic vulnerability among strains. These findings underscore the importance of selecting genetically matched wild-type controls. (Stroke. 2000;31:2707-2714.)

Increased Apoptosis and Inflammation after Focal Brain Ischemia in Mice Lacking Connexin43 in Astrocytes

“…Moreover, previous reports have demonstrated a significantly different stroke volume between different strains of wild-type mice, and variations of vascular anatomy or intrinsic factors yet to be determined were assumed to contribute to these differences. 37,38 Brain injury was assessed at 4 days after stroke. After ischemic insults, focal pan-necrosis occurs immediately 39 and apoptosis follows in 1 to 2 days.…”

Rodent models of focal stroke: Size, mechanism, and purpose

“…C57BL/6 have poorly developed posterior communicating arteries, 71,75,76 which will limit collateral flow to the territory distal to an occluded MCA. However, the degree of development of the circle of Willis does not strictly correlate with distal blood flow 71,72 or with infarct size. 77 Of the commonly used mice strains, C57BL/6 and BALB/c are more resistant than Sv129 and FVB/N mice to kainite-induced excitotoxic hippocampal damage, 78 which is the inverse pattern of sensitivity to suture-induced MCAo.…”

“…71 Interestingly, in distal MCAo (see below), BALBc mice have larger strokes than C57BL/6 and Sv129 strains. [72][73][74] There are strain differences in arterial collaterals and sensitivity to excitotoxic cell death that may partially account for these differences. C57BL/6 have poorly developed posterior communicating arteries, 71,75,76 which will limit collateral flow to the territory distal to an occluded MCA.…”

“…Most investigators do not divide the zygomatic arch as was originally described, but the surgical approach still involves skillful separation of the parotid gland and temporalis muscle and a narrow craniotomy over the MCA. 44,72,73,90,91 The ischemic damage includes much of the striatum, subcortical white matter, and ipsilateral cortex ( Table 2). The second technique involves occlusion of the MCA on the surface of the brain, and bilateral common carotid occlusion-the three-vessel occlusion model.…”

Investigation of Epidermal Growth Factor, Tumor Necrosis Factor-alpha and Thioredoxin System in Rats Exposed to Cerebral Ischemia

“…Permanent occlusion of MCAO was achieved by using the described method in the literature (8)(9)(10). Briefly, left common carotid artery was exposed through a midline vertical incision under anaesthesia (100 mg/kg ketamine and 5 mg/ kg xylazine).…”