PROCEDURAL AND STRAIN-RELATED VARIABLES SIGNIFICANTLY AFFECT OUTCOME IN A MURINE MODEL OF FOCAL CEREBRAL-ISCHEMIA

THE RECENT AVAILABILITY of transgenic mice has led to a burgeoning num ber of reports describing the effects of specific gene products on the pathophysiology of stroke. Although focal cerebral ischemia models in rats have been well described, descriptions of a murine model of midd le cerebral artery occlusion are scant and sources of potential experi mental variability remain undefined. We hypothesized that slight techn ical modifications would produce widely discrepant results in a murine model of stroke and that controlling surgical and procedural conditio ns could lead to reproducible physiological and anatomic stroke outcom es. To test this hypothesis, we established a murine model that would permit either permanent or transient focal cerebral ischemia by intral uminal occlusion of the middle cerebral artery. This study provides a detailed description of the surgical technique and reveals important d ifferences among strains commonly used in the production of transgenic mice. In addition to strain-related differences, infarct volume, neur ological outcome, and cerebral blood flow appear to be importantly aff ected by temperature during the ischemic and postischemic periods, mou se size, and the size of the suture that obstructs the vascular lumen. When these variables were kept constant, there was remarkable uniform ity of stroke outcome. These data emphasize the protective effects of hypothermia in stroke and might help to standardize techniques among d ifferent laboratories to provide a cohesive framework for evaluating t he results of future studies in transgenic animals.