title: Characterization of a 3-vessel occlusion model for the induction of complete global cerebral ischemia in mice.
abstract: Existing murine models of global cerebral ischemia are technically challenging thereby hampering the use of genetically engineered mice to study cardiac arrest-induced brain damage. We therefore investigated, if disconnecting the cerebral circulation from vertebral collateral blood flow by proximal occlusion of the basilar artery together with temporary bilateral common carotid artery occlusion (BCCAo) may be a more feasible approach. C57/Bl6 mice were anesthetized and the basilar artery was occluded through a ventral approach. Ten days later BCCAo was performed for 8-14min. Increasing durations of ischemia resulted in enhanced neuronal cell death in cortex, striatum, and hippocampus (22-63%) and increased neurological dysfunction and mortality (0-36%). Following 10min of BCCAo, the duration of global ischemia with the most favorable mortality/neuronal cell death ratio, hippocampal damage started 6h after the insult while cortical and striatal damage was delayed by at least 24h. No further loss of neuronal cells was observed later than 3 days. The proposed two-step approach resulted in complete cerebral ischemia and caused neuronal damage with high reproducibility and small variability. In combination with transgenic and knock-out mice this technically feasible model may help to extend our knowledge on the pathophysiology of cardiac arrest-induced brain damage.
authors.affiliation: Institute for Surgical Research, University of Munich Medical Center Grosshadern, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Serge C
authors.initials: SC
authors.lastname: Thal
authors.forename: Simone E
authors.initials: SE
authors.lastname: Thal
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Plesnila
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D003342:Corpus Striatum / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000473:pathology; D013997:Time Factors