Characterization of a 3-vessel occlusion model for the induction of complete global cerebral ischemia in mice

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 8-14 min. 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 10 min of BCCAo, the duration of global ischemia with the most favorable mortality/neuronal cell death ratio, hippocampal damage started 6 h after the insult while cortical and striatal damage was delayed by at least 24 h. 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.

Research highlights▶ New model of global cerebral ischemia in mice. ▶ Disconnecting the cerebral circulation from vertebral collateral blood flow by proximal basilar artery occlusion followed by 10 min bilateral carotid artery occlusion 10 days later. ▶ The model is technically feasible, has an acceptable mortality, and results in highly reproducible delayed hippocampal, cerebral, and striatal cell death.