title: 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 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.
authors.affiliation: Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Nordre Ringvej 69, 2600, Glostrup, Denmark. stine.spray@regionh.dk.
authors.forename: Stine
authors.identifier: http://orcid.org/0000-0002-9381-7209
authors.initials: S
authors.lastname: Spray
authors.affiliation: Department of Clinical Experimental Research, Glostrup Research Institute, Rigshospitalet, Glostrup, Nordre Ringvej 69, 2600, Glostrup, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D020212:Carotid Artery Injuries / Q000150:complications; D016923:Cell Death; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology*; D007022:Hypotension / Q000150:complications; D002546:Ischemic Attack, Transient / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology
keywords: Delayed mortality; Delayed neuronal cell death; Exploratory behavior assessment; Global cerebral ischemia; Mouse model