areas. Focal ischemia models They are divided into techniques including reperfusion of the ischemic tissue (transient focal cerebral ischemia) and those without reperfusion (permanent focal cerebral ischemia). The following models are established : Endothelin-1 -induced constriction of arteries and veins Middle cerebral artery occlusion (MCAO) MCAO avoiding craniotomy Embolic middle cerebral artery occlusion Endovascular filament middle cerebral artery occlusion (transient or permanent) MCAO involving craniotomy Permanent transcranial middle cerebral artery occlusion Transient transcranial middle cerebral artery occlusion Direct tissue damage Cerebrocortical photothrombosis Endothelin-1 -induced constriction of arteries and veins Endothelin-1 is a potent vasoconstrictor which is produced endogenously during ischemic stroke and which contributes to overall loss of cells and disability. Exogenous endothelin-1 can also be used to induce stroke and cell death after sustained vasoconstriction with reperfusion. It can be microinjected to induce focal stroke in small tissue volumes (e.g., cortical grey matter, white matter or subcortical tissue) or after injection near the Middle cerebral artery. It is often used as a model of focal stroke to evaluate candidate pro-regenerative therapies. One advantage of this model of stroke is that it causes highly reproducible infarcts. Another benefit is that it can be used in elderly rats with only very low resulting mortality. Embolic middle cerebral artery occlusion Middle cerebral artery (MCA) occlusion is achieved in this model by injecting particles like blood clots (thrombembolic MCAO) or artificial spheres into the carotid artery of animals as an animal model of ischemic stroke. Thrombembolic MCAO is achieved either by injecting clots that were formed in vitro or by endovascular instillation of thrombin for in situ clotting . The thrombembolic model is closest to the pathophysiology of human cardioembolic stroke. When injecting spheres into the cerebral circulation, their size determines the pattern of brain infarction: Macrospheres (300–400 µm) induce infarcts similar to those achieved by occlusion of the proximal MCA , whereas microsphere (~ 50 µm) injection results in distal, diffuse embolism . However, the quality of MCAO – and thus the volume of brain infarcts – is very variable, a fact which is further aggravated by a certain rate of spontaneous lysis of injected blood clots. Endovascular filament middle cerebral artery occlusion The technique of endovascular filament (intraluminal suture) MCAO as an animal model of ischemic stroke was described first by Koizumi . It is applied to rats and mice. A piece of surgical filament is introduced into the internal carotid