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Stroke is a leading cause of death and disability. Animal models of stroke have been developed as a means to characterize the pathophysiology of ischemia and evaluate therapeutic treatments to alleviate brain damage and the attendant neurologic deficits. Mice offer investigators a way to address specific gene effects including mutations, complete deletions and overexpression. A plethora of mouse models are available to the investigator including surgical occlusion of major cerebral arteries, intraluminal filament occlusion, thromboembolic, photothrombotic and stroke induced by pharmacologic vasoconstrictors. This chapter describes the origins of these models, technical aspects of procedures, and their strengths and weaknesses. We also highlight the utility of these models for investigating genetic and pharmacologic strategies to protect the brain. Last, we have a special focus on mouse models of ischemic tolerance, whereby brief, non-harmful ischemic episodes preceding a prolonged ischemic event reduce damage, and we highlight the emerging cell and molecular mediators thereof.

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