Animal models of ischemic stroke are procedures inducing cerebral ischemia. The aim is the study of basic processes or potential therapeutic interventions in this disease, and the extension of the pathophysiological knowledge on and/or the improvement of medical treatment of human ischemic stroke. Ischemic stroke has a complex pathophysiology involving the interplay of many different cells and tissues such as neurons, glia, endothelium, and the immune system. These events cannot be mimicked satisfactorily in vitro yet. Thus a large portion of stroke research is conducted on animals. Overview Several models in different species are currently known to produce cerebral ischemia. Global ischemia models, both complete and incomplete, tend to be easier to perform. However, they are less immediately relevant to human stroke than the focal stroke models, because global ischemia is not a common feature of human stroke. However, in various settings global ischemia is also relevant, e.g. in global anoxic brain damage due to cardiac arrest. Different species also vary in their susceptibility to the various types of ischemic insults. An example is gerbils. They do not have a Circle of Willis and stroke can be induced by common carotid artery occlusion alone. Mechanisms of inducing ischemic stroke Some of the mechanisms which have been used are: Complete global ischemia Decapitation Aorta/vena cava occlusion External neck tourniquet or cuff Cardiac arrest Incomplete global ischemia Hemorrhage or hypotension Hypoxic ischemia Intracranial hypertension and common carotid artery occlusion Two-vessel occlusion and hypotension Four-vessel occlusion Unilateral common carotid artery occlusion (in some species only) Focal cerebral ischemia Endothelin-1-induced constriction of arteries and veins Middle cerebral artery occlusion Spontaneous brain infarction (in spontaneously hypertensive rats) Macrosphere embolization Multifocal cerebral ischemia Blood clot embolization Microsphere embolization Photothrombosis Hypoxic Ischemia models One of the most commonly used animal models of hypoxic ischemia was originally described by Levine in 1960 and later refined by Rice et al., in 1981. This approach is useful to study hypoxic ischemia in the developing brain, since newborn rat pups are utilized in this model. Briefly, 7 day old rat pups undergo a permanent unilateral carotid artery ligation with a subsequent 3 hour exposure to a hypoxic environment (8% oxygen). This model creates a unilateral infarct in the hemisphere ipsilateral to the ligation, since the hypoxia alone is subthreshold for injury at this age. The area of injury is typically concentrated in periventricular regions of the brain, especially cortical and hippocampal