Animal models of stroke

Abstract

Stroke is a leading cause of morbidity and mortality worldwide and in China. In China, stroke was the leading cause of death and DALYs in 2017. 1 Age-standardized DALYs per 100 000 population decreased by 33.1% for stroke. Of all strokes, up to 80% to 85% are ischemic, 2 which can be subdivided based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification. 3 Large vessel atherosclerosis of cervical or proximal intracranial vessels comprises a major cause of acute stroke, ranging from 30% to 43%, while 20%-31% is caused by cardioembolism. Approximately 10%-23% of all strokes are lacunar in type, which are mainly caused by diabetes and hypertension. Some additional unusual causes, such as vasculopathy or extracranial artery dissection, account for 2%-11%. 4,5 Approximately 5%-21% of strokes are hemorrhagic, and their common causes are hypertension and vascular malformations. 6 Strokes are heterogeneous diseases, and in vivo models are essential tools to mimic these processes for investigating pathophysiology and therapeutic approaches. Each model has its unique strengths and weaknesses (Tables 1 and 2). Only when we realize their importance can we choose the best one for an investigation, with "best" referring to that which most closely approximates a certain aspect of the multiple facets of strokes.

A Novel Thromboplastin-Based Rat Model of Ischemic Stroke

“…Currently, in thromboembolic stroke modeling, the clot is injected through the external carotid artery in most cases. A modification of thromboembolic MCAO model developed by Zhang RL (1997) is most commonly used in the current studies [ 28 , 29 ]. However, this method requires an expensive operating microscope, which significantly limits its use.…”

An Optimal Animal Model of Ischemic Stroke Established by Digital Subtraction Angiography-Guided Autologous Thrombi in Cynomolgus Monkeys

“…In addition, using autologous blood clots allows for studying thrombolytic drugs. However, the previous animal models of MCAO have shown various shortcomings, mainly such as large trauma, high animal mortality, uncertainty of embolus size, travel path, and final retention position and inability to effectively evaluate the long-term neurological function of model animals ( 14 , 17 , 20 , 38 – 40 ). In this study, based on the vascular diameter detected with imaging, each thrombus was microscopically divided into emboli of an appropriate size.…”

“…Most stroke experiments are performed in small animals (e.g., mice, rats, and rabbits) ( 14 ). The use of small animals has obvious advantages—lower cost and greater acceptability from an ethical perspective—compared with larger animals ( 41 ).…”

“…To date, several reproducible animal models of permanent and transient focal cerebral ischemia have been established, in which a brain-supplying artery is occluded by mechanical devices, such as sutures, clips, and hooks, pharmacological agents, or delivery of blot clots ( 10 – 14 ). However, many of these models poorly mimic clinical thrombus formation, decreasing their clinical utility.…”

Novel Animal Model of Spontaneous Cerebral Petechial Hemorrhage Using Focused Ultrasound in Rats

“…This hemorrhage is essentially different from a petechial hemorrhage. In addition, petechial hemorrhages have been reported as part of the accompanying bleeding in cerebral infarction and head trauma models in animal studies that were not focused on petechial hemorrhages [ 4 , 5 , 6 , 7 ]. Therefore, animal models that can faithfully implement and recapitulate petechial hemorrhages for its study are needed.…”