Improved assessment of outcomes following transient global cerebral ischemia in mice.

Abstract

Mouse models of global cerebral ischemia (GCI) allow experimental examination of cerebral pathophysiology in genetically modified mice and fast screening of new treatment strategies. Various surgical protocols of GCI-induction in mice have been published; however, many of these studies are hindered by limited neurological assessment protocols and present insufficient reporting of the cumulative survival rate. Therefore, we aim at developing a reproducible and easily implementable model of transient GCI in mice with minimal impact on normal mouse behavior. GCI was induced in male C57BL/6 mice by bilateral occlusion of the common carotid arteries for 10min combined with isoflurane-induced hypotension which resulted in severe reduction in the cerebral blood flow of the forebrain. Sham operation served as a control. Exploratory behavior was evaluated in a home-cage environment the day before and again daily for up to 7days after GCI or sham operation and was found to be significantly decreased 1-7days after GCI compared to sham. Furthermore, we found delayed neuronal cell death in the frontal cortex and hippocampus 5 and 7days after GCI but not at day 3 or after sham operation. The survival rate at day 7 was 100% after sham operation and 42% after GCI. The model of GCI in mice presented in this study compromises the exploratory behavior and resembles the cerebral damage and mortality rate seen after cardiac arrest and/or GCI in man, and is therefore a good model to use for studies of GCI pathophysiology.