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Improved assessment of outcomes following transient global cerebral ischemia in mice

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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 10 min 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 7 days after GCI or sham operation and was found to be significantly decreased 1-7 days after GCI compared to sham. Furthermore, we found delayed neuronal cell death in the frontal cortex and hippocampus 5 and 7 days 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.

Original languageEnglish
JournalExperimental Brain Research
Volume234
Issue number7
Pages (from-to)1925-34
ISSN0014-4819
DOIs
Publication statusPublished - Jul 2016

ID: 46389822