Rat Model of Global Cerebral Ischemia: The Two-Vessel Occlusion (2VO) Model of Forebrain Ischemia

Abstract

Animal models of brain ischemia can be divided into focal and global brain ischemia. Among global (often referred to as forebrain) ischemia animal models, the 2-vessel occlusion (2VO) and 4-vessel occlusion (4VO) models in rats are most frequently employed in the studies of molecular mechanisms of neuronal damage after brain ischemia followed by reperfusion. This chapter mainly discusses the rat 2VO model. In this model, reversible forebrain ischemia is produced by bilateral common carotid artery (CCA) occlusion combined with systemic hypotension (50 mmHg) sufficient to induce brain ischemia. This ischemia and reperfusion model affects widespread areas of the forebrain brain. There are two chief histopathological changes in this 2VO ischemia model: (1) selective neuronal vulnerability; typically CA1 pyramidal neurons of the hippocampus are most vulnerable, followed by dorsoventral striatal small- and medium-sized neurons, and pyramidal neurons in the layers 3–4 of the neocortex; and (2) delayed neuronal death, i.e., neuronal death does not occur immediately after transient ischemic episode, but takes place after 2–3 days of reperfusion. This model during the surgical procedure requires artificially maintenance of: (1) rectal and brain temperatures at 37 °C; (2) the mean arterial pressure (MABP); and (3) blood gases. This 2VO ischemia model has the advantage of a one-step surgical procedure that produces high-grade forebrain ischemia. The reproducibility of the ischemic histopathological damage of this model is more than 90%. This animal model is also suitable for molecular, biochemical and physiological studies, as well as for evaluation of neuroprotective procedures and agents.