Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusio...Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.展开更多
Despite the impressive efficacies demonstrated in preclinical research,hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotec-tion for ischemic stroke in human clinical trials.Lack ...Despite the impressive efficacies demonstrated in preclinical research,hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotec-tion for ischemic stroke in human clinical trials.Lack of a powerful animal model for human ischemic stroke could be a major reason for the failure to develop successful neuroprotective drugs for ischemic stroke.This review recapitulates the available cerebral ischemia animal models,provides an anatomical comparison of the circle of Willis of each species,and describes the functional assessment tests used in these ischemic stroke models.The distinct differences between human ischemic stroke and experimental stroke in available animal models is explored.Innovative animal models more closely resembling human strokes,better techniques in functional out-come assessment and better experimental designs generating clearer and stronger evidence may help realise the development of truly neuroprotective drugs that will benefit human ischemic stroke patients.This may involve use of newer molecules or revisiting earlier studies with new experimental designs.Translation of any resultant successes may then be tested in human clinical trials with greater confidence and optimism.展开更多
基金supported by the 2013 Inje University Research Grant
文摘Experimental stroke research commonly employs focal cerebral ischemic rat models （Bederson et al., 1986a; Longa et al., 1989）. In human patients, ischemic stroke typically results from thrombotic or embolic occlusion of a major cerebral artery, usually the mid- dle cerebral artery （MCA）. Experimental focal cerebral ischemia models have been employed to mimic human stroke （Durukan and Tatlisumak, 2007）. Rodent models of focal cerebral ischemia that do not require craniotomy have been developed using intraluminal suture occlusion of the MCA （MCA occlusion, MCAO） （Rosamond et al., 2008）. Furthermore, mouse MCAO models have been wide- ly used and extended to genetic studies of cell death or recovery mechanisms （Liu and McCullough, 2011）. Genetically engineered mouse stroke models are particularly useful for evaluation of isch- emic pathophysiology and the design of new prophylactic, neuro- protective, and therapeutic agents and interventions （Armstead et al., 2010）. During the past two decades, MCAO surgical techniques have been developed that do not reveal surgical techniques for mouse MCAO model engineering. Therefore, we compared MCAO surgical methods in rats and mice.
基金Science and Engineering Research Board,Grant/Award Number:CRG/2019/002076Council of Scientific and Industrial Research,Grant/Award Number:09/805(0012)/2019-EMR-I。
文摘Despite the impressive efficacies demonstrated in preclinical research,hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotec-tion for ischemic stroke in human clinical trials.Lack of a powerful animal model for human ischemic stroke could be a major reason for the failure to develop successful neuroprotective drugs for ischemic stroke.This review recapitulates the available cerebral ischemia animal models,provides an anatomical comparison of the circle of Willis of each species,and describes the functional assessment tests used in these ischemic stroke models.The distinct differences between human ischemic stroke and experimental stroke in available animal models is explored.Innovative animal models more closely resembling human strokes,better techniques in functional out-come assessment and better experimental designs generating clearer and stronger evidence may help realise the development of truly neuroprotective drugs that will benefit human ischemic stroke patients.This may involve use of newer molecules or revisiting earlier studies with new experimental designs.Translation of any resultant successes may then be tested in human clinical trials with greater confidence and optimism.
