Brain Research 868 (2000) 14–21 www.elsevier.com / locate / bres Research report A comparison of strain-related susceptibility in two murine recovery models of global cerebral ischemia a,d b c b John C. Wellons III , Huaxin Sheng , Daniel T. Laskowitz , G. Burkhard Mackensen , a,b a,b, * Robert D. Pearlstein , David S. Warner a Department of Surgery ( Division of Neurosurgery), Duke University Medical Center, Durham, NC 27710, USA b Department of Anesthesiology, Duke University Medical Center, Box 3094, Durham, NC 27710, USA c Department of Medicine ( Division of Neurology), Duke University Medical Center, Durham, NC 27710, USA d Cerebrovascular Disease Research Fellow, Duke Center for Cerebrovascular Disease, Duke University Medical Center, Durham, NC 27710, USA Accepted 1 March 2000 Abstract 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 (2VO1Hypo; mean arterial pressure53062 mmHg) for 10–20 min. Ventilation and pericranial temperature were controlled. Cerebral 14 blood flow (CBF) was determined by C-iodoantipyrine autoradiography. Histologic damage in forebrain structures was measured 3 days post-ischemia. During 2VO1Hypo, 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 2VO1Hypo. CBF was less in the 2VO1Hypo 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 2VO1Hypo model but not with 2VO alone. The 2VO and 2VO1Hypo 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 2VO1Hypo 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.  2000 Elsevier Science B.V. All rights reserved. Theme: Disorders of the nervous system Topic: Ischemia Keywords: Mouse; Brain; Ischemia; Transgenic; Histology; Cerebrovascular anatomy 1. Introduction places some limitation on the utility of these constructs, understanding of mechanistic responses to ischemic insults Recent advances in murine reproductive biology have can be examined in the absence of non-specific effects allowed introduction of murine mutants into experimental often presented by use of pharmacologic probes. brain research protocols. Either insertion or disruption of Numerous investigators have demonstrated that the the genetic code in the murine genome allows us to study murine strain used to create transgenic or knockout ani- the effects of a single protein in models of focal or global mals plays an important role in defining the outcome from ischemia. Although ontogenetic adaptation to mutations the ischemic or traumatic insult under study. For example, Maeda et al. [9] have shown that C57Bl/6 mice have a larger proportion of brain dependent upon middle cerebral *Corresponding author. Tel.: 11-919-684-6633; fax: 11-919-684- artery perfusion than do SV129 mice and, thus, develop 6692. E-mail address: warne002@mc.duke.edu (D.S. Warner) larger infarcts in response to a standardized interval of 0006-8993 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)02216-2