Differences in vulnerability to permanent focal cerebral ischemia among 3 common mouse strains

Background and Purpose-Genetically engineered mice are used to study the ro le of single genes in cerebral ischemia, but inherent, strain-dependent dif ferences in neuronal vulnerability may affect experimental end points. To e xamine this possibility, tissue injury resulting from focal ischemia and it s relationship to cerebral hemodynamics;Were determined in 3 common mutant mouse strains. Methods-Permanent middle cerebral artery ligation was performed in male C57 BL/6J, Balb/C, and 129X1/SvJ mice. Mean arterial blood pressure, blood gase s, basal and postischemic cortical blood flow ([C-14]iodoantipyrine autorad iography and laser-Doppler flowmetry), posterior communicating artery paten cy, 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 ische mic cortex was 6% to 7% of preischemic flow in every strain. Despite simila r hemodynamics, cortical infarcts in Balb/C mice were 3-fold larger than th ose in 129X1/SvJ and C57BL/6J mice; infarct size in the latter 2 strains wa s not significantly different. The posterior communicating artery was eithe r poorly developed or absent in > 90% of the Balb/C and C57BL/6J but in < 5 0% of the 129X1/SvJ mice. Conclusions-The extent of ischemic injury differed markedly between the 3 s trains. The presence and patency of posterior communicating arteries, altho ugh variable among strains, did not affect preischemic or postischemic cort ical blood flow or bear any relationship to ischemic injury. Therefore, int rinsic factors, other than hemodynamic variability, may contribute to the d ifferences in ischemic vulnerability among strains. These findings undersco re the importance of selecting genetically matched wild-type controls.