A comparison of strain-related susceptibility in two murine recovery models of global cerebral ischemia.
Genetically engineered mice are increasingly important in stroke research. The strains on which these constructs are built are known to have inherent differential sensitivities to ischemic insults. This has been largely attributed to differences in vascular anatomy. This study compared the outcome from forebrain ischemia in two common murine background strains using two different types of ischemic insult. C57Bl/6 and SV129 mice were subjected to two vessel (bilateral carotid) occlusion (2VO) or 2VO plus systemic hypotension (2VO+Hypo; mean arterial pressure=30+/-2 mmHg) for 10-20 min. Ventilation and pericranial temperature were controlled. Cerebral blood flow (CBF) was determined by 14C-iodoantipyrine autoradiography. Histologic damage in forebrain structures was measured 3 days post-ischemia. During 2VO+Hypo, the EEG became isoelectric in all animals. During 2VO alone, EEG isoelectricity occurred in 73% of C57Bl/6 and 50% of SV129 mice. Forebrain CBF was reduced to a similar extent in both strains. Greater CBF variability was seen with 2VO alone versus 2VO+Hypo. CBF was less in the 2VO+Hypo model. SV129 mice had wider posterior communicating but smaller basilar artery diameters. With or without hypotension, SV129 mice had markedly less severe histologic damage than C57Bl/6 mice. A time-dependent increase in histologic damage was demonstrated in the 2VO+Hypo model but not with 2VO alone. The 2VO and 2VO+Hypo models produced similar magnitudes of histologic injury in C57Bl/6 mice subjected to 10-min ischemia. SV129 mice were resistant to ischemia in either model. The 2VO+Hypo model produced a more uniform severity of ischemia as defined by CBF and EEG examination. Despite this, the murine strain had a substantially greater impact on histologic outcome than did cerebrovascular anatomy or the type of model used to produce the ischemic insult.
Wellons, JC; Sheng, H; Laskowitz, DT; Mackensen, GB; Pearlstein, RD; Warner, DS
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