Selective middle cerebral artery occlusion in the rabbit: Technique and characterization with pathologic findings and multimodal MRI

Abstract

BackgroundA reliable animal model of ischemic stroke is vital for pre-clinical evaluation of stroke therapies. We describe a reproducible middle cerebral artery (MCA) embolic occlusion in the French Lop rabbit characterized with multimodal MRI and histopathologic tissue analysis. New methodFluoroscopic-guided microcatheter placement was performed in five consecutive subjects with angiographic confirmation of MCA occlusion with autologous clot. Multimodal MRI was obtained prior to occlusion and up to six hours post after which repeat angiography confirmed sustained occlusion. The brain was harvested for histopathologic examination. ResultsAngiography confirmed successful MCA catheterization and durable (>6 h) MCA occlusion in all animals. There was increase of ADC volume over time and variable final core volume presumably related to individual variation in collateral flow. FLAIR hyperintensity indicative of cytotoxic edema and parenchymal contrast enhancement reflective of blood brain barrier disruption was observed over time. Tissue staining of the ischemic brain showed edema and structural alterations consistent with infarction. Comparison with existing methodsThis study describes a technique of selective catheterization and embolic occlusion of the MCA in the rabbit with MRI characterization of evolution of ischemia in the model. ConclusionsWe demonstrate the feasibility of a rabbit model of embolic MCA occlusion with angiographic documentation. Serial MR imaging demonstrated changes comparable to those observed in human ischemic stroke, confirmed histopathologically.