Guidelines for Using Mouse Global Cerebral Ischemia Models

Mouse models of global cerebral ischemia are essential tools to study the molecular mechanisms involved in ischemic brain damage. The availability of genetically engineered mice allows examination of the role of specific proteins in brain pathology processes. However, relative to rat models, mouse global brain ischemia models are technically more challenging to produce. It is important to emphasize that occlusion of two carotid arteries only is highly inefficient to produce consistent brain damage in mice. This is mainly due to high variability in their vascular anatomy. Several approaches were developed to achieve sufficient reduction of blood flow in the mouse brain that led to consistent ischemic brain damage. We describe here the mouse ischemic models most frequently utilized in research laboratories to test the effect of genetically manipulated proteins of interest on ischemic brain injury or to assess a drug effect on ischemia-induced brain damage. The most common approach used is the bilateral common carotid occlusion that is combined with either occlusion of a third artery or with concomitant reduction of mean arterial blood pressure. Furthermore, a four-vessel occlusion model can be used or even a cardiac arrest model that has been developed for mouse. All these models have specific problems, advantages, and clinical relevance. Thus, the feasibility of using a particular model depends on the goal of the study and the outcome parameters assessed. Overall, the mouse models are valuable since they allow the study of ischemia-induced molecular mechanisms utilizing transgenic animals and also evaluate the effect of new neuroprotective compounds.