Preclinical animal studies in ischemic stroke: Challenges and some solutions |
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Authors: | Sunil K Narayan Simy Grace Cherian Prakash Babu Phaniti Saravana Babu Chidambaram A Hannah Rachel Vasanthi Murugesan Arumugam |
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Institution: | Comprehensive Stroke Care and Neurobiology Centre,Department of Neurology,Jawaharlal Institute of Postgraduate Medical Education and Research,Puducherry,India;Department of Biotechnology&School of Medical Sciences,University of Hyderabad,Hyderabad,India;Department of Pharmacology,JSS Medical College,Mysore,India |
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Abstract: | Despite the impressive efficacies demonstrated in preclinical research, hundreds of potentially neuroprotective drugs have failed to provide effective neuroprotection 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 outcome 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. |
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Keywords: | cerebral ischemia circle of Willis focal ischemic models functional assessment tests neuroprotection preclinical model |
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