TABLE 3.

The development of the generation of stroke models

Stroke models	Time	Authors	Approaches	Insult regions	Technical improvements
Ischemic stroke models
Global ischemic stroke
Incomplete global brain ischemia
4‐VO model	1979	Pulsi‐Purkinjenelli and Brierley	Permanent occlusion of vertebral arteries and reversible occlusion of CCA	Forebrain ischemia	Vertebral artery was electro‐cauterized at the second vertebra under microscope for highly reproducible forebrain ischemia model
2‐VO model	1972	Eklof and Siesjo	Occlusion of bilateral carotid arteries alone or combined with reductions in the mean arterial blood pressure	Permanent BCAO could produce a model for chronic cerebral hypoperfusion‐related neurodegenerative diseases Transient BCAO with a reduction in mean arterial blood pressure could establish a forebrain ischemic model	Modifying the time interval between the ligations of the BCA could ameliorate lethal effects BCAO alone could cause severe ischemic insults of the brain in SHRs
Complete global brain ischemia (CGBI)
Aorta/vena cava occlusion model	1989	Hashimoto	Ascending aorta occlusion combined with bypass formation between the aorta and right atrium	Global brain ischemia	Using aortic and inferior vena cava occlusion balloons avoids surgical invasion of the thorax Aorta occlusion without vena cava occlusion is more suitable for short‐term study on CGBI
Ventricular fibrillation (VF)	1981	Todd	Shocking the heart and urgent cardiopulmonary resuscitation	Global brain ischemia
Chemical or gas hypoxia	2011	Yu, Xinge	Nitrogen gas hypoxia	Optic tectum	The addition of sodium sulfite is introduced for a chemical hypoxia
Focal ischemic stroke
Transcranial occlusion	1981	Tamura	Occluding the stem of the proximal MCA through a small subtemporal craniectomy	The frontal cortex, the lateral part of the neostriatum, the sensorimotor and the auditory cortex in most animals	tandem occlusion of the distal MCA and ipsilateral CCA; combined occlusion of the MCA and bilateral CCA (3‐VO models)
Endovascular filament middle cerebral artery occlusion (MCAo)	1985	Koizumi	Introducing a filament with a round tip from the ECA into the ICA and advancing it to block the origin of the MCA	One hour after occlusion, the ischemic cells are slightly scattered, whereas occlusion for more than 3 h causes severe ischemic lesions in the anterior neocortex and the lateral part of the caudate putamen supplied by the MCA After permanent MCA occlusion, irreversible injury appears first in the caudoputamen and then spreads to the cortex	Filaments coated with silicone, poly‐L‐lysine or paraffin reduce interanimal variability The diameter of the suture tip and the insertion distance of the suture affect reproductivity ECG, LDF and MRI can effectively guide filament placement
Embolic occlusion	1982	Kudo	Intracarotid injection of thromboembolus and artificial spheres	Parietotemporal cortex, hippocampus, thalamic striatum, and even a small proportion of the contralateral hemisphere	Utilizing microcatheter and LDF could ensure the occlusion of MCA more precise
Endothelin‐1 occlusion	1995	Reid	Administrating ET‐1 to the surgically exposed MCA	Caudate nucleus, the genu of the corpus callosum, and the cortex lying wholly within the territory of the MCA	Stereotaxic injection of ET‐1 into the superficial cortex adjacent to the MCA can establish the similar infarct volumes Stereotactic injection of ET‐1 into the cortex can be used to induce infarction in other specific brain regions, such as internal capsule ischemia and frontoparietal cortex infarction
Photothrombosis model	1985	Waston	Injecting photosensitive dye (rose bengal, erythrosin B) into circulation and then to irradiate the intact cranium of a specific area with a certain range of wavelength laser beams	Ipsilateral cortex	The laser beam can directly irradiate a certain vessel to produce cerebral ischemia in its supply regions. Photochemical MCA occlusion and reperfusion can be controlled by utilizing a 2‐laser system Rose bengal plus thrombin aim to enhance the sensitivity to rt‐PA treatment The application route of the photosensitive dye, illumination and stereotactic parameters is refined
Intracerebral hemorrhage
Whole blood injection model	1982	Ropper and Zervas	Injecting donor/autologous arterial blood into the caudate nucleus	Caudate nucleus	injection of 0.2 mL of autologous blood into the caudate nucleus; micropump connected to a stereotactic syringe, injecting constantly and slowly; double blood injection method to prevent the blood reflux and hematoma expand
Collagenase model	1990	Rosenberg	Stereotactic injection of bacterial collagenase into brain regions	Specific cerebral parenchyma or intraventricular hemorrhage	Easy to control the size of the hematoma by adjusting the amount of collagenase