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 an which these constructs are built are known to have inherent differential sensitivities to ischemic insults. This has been largely attri buted to differences in vascular anatomy. This study compared the outcome f rom forebrain ischemia in two common murine background strains using two di fferent types of ischemic insult. C57Bl/6 and SV129 mice were subjected to two vessel (bilateral carotid) occlusion (2VO) or 2VO plus systemic hypoten sion (2VO+Hypo; mean arterial pressure = 30+/-2 mmHg) for 10-20 min. Ventil ation and pericranial temperature were controlled, Cerebral blood flow (CBF ) was determined by C-14-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 isoelectr icity occurred in 73% of C57Bl/6 and 50% of SV129 mice. Forebrain CBF was r educed to a similar extent in both strains. Greater CBF variability was see n with 2VO alone versus 2VO+Hypo. CBF was less in the 2VO+Hypo model. SV129 mice had wider posterior communicating but smaller basilar artery diameter s. With or without hypotension, SV129 mice had markedly less severe histolo gic damage than C57Bl/6 mice, A time-dependent increase in histologic damag e was demonstrated in the 2VO+Hypo model but not with 2VO alone. The 2VO an d 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 mon uniform severity of isc hemia as defined by CBF and EEG examination. Despite this, the murine strai n had a substantially greater impact on histologic outcome than did cerebro vascular anatomy or the type of model used to produce the ischemic insult. (C) 2000 Elsevier Science B.V. All rights reserved.