A Modified Transorbital Baboon Model of Reperfused Stroke

Abstract

This chapter describes a modified transorbital baboon model of reperfused stroke. Rodent models are the most commonly used animal models of cerebral ischemia used in preclinical testing. The most commonly used model of ischemia–reperfusion injury involves insertion of a silicon-coated suture into the internal carotid artery and advancing it intracranially to occlude middle cerebral artery blood flow. A model of reperfused nonhuman primate stroke that utilized, through a transorbital approach, unilateral internal carotid artery and bilateral anterior cerebral artery occlusion is presented. The investigation of a humanized monoclonal antibody, HuEP5C7, which competitively binds E-selectin and P-selectin, critical adhesion molecules implicated in both microvascular failure and inflammation following cerebral ischemia is presented. Eighteen adult baboons were randomized to receive either HuEP5C7 or placebo immediately following a 1-h ischemic period. Histologic examination of the infarct was analyzed to determine tissue levels of P- and E-selectin. It is suggested that such models provide a testing ground for novel neuroprotective agents without putting patients at risk for potential negative side effects.