Preclinical stroke research - advantages and disadvantages of the most common rodent models of focal ischaemia

Macrae, I.M. (2011) Preclinical stroke research - advantages and disadvantages of the most common rodent models of focal ischaemia. British Journal of Pharmacology, 164(4), pp. 1062-1078. (doi: 10.1111/j.1476-5381.2011.01398.x)




This review describes the most commonly used rodent models and outcome measures in preclinical stroke research and discusses their strengths and limitations. Most models involve permanent or transient middle cerebral artery occlusion with therapeutic agents tested for their ability to reduce stroke-induced infarcts and improve neurological deficits. Many drugs have demonstrated preclinical efficacy but, other than thrombolytics, which restore blood flow, none have demonstrated efficacy in clinical trials. This failure to translate efficacy from bench to bedside is discussed alongside achievable steps to improve the ability of preclinical research to predict clinical efficacy: (i) Improvements in study quality and reporting. Study design must include randomization, blinding and predefined inclusion/exclusion criteria, and journal editors have the power to ensure statements on these and mortality data are included in preclinical publications. (ii) Negative and neutral studies must be published to enable preclinical meta-analyses and systematic reviews to more accurately predict drug efficacy in man. (iii) Preclinical groups should work within networks and agree on standardized procedures for assessing final infarct and functional outcome. This will improve research quality, timeliness and translational capacity. (iv) Greater uptake and improvements in non-invasive diagnostic imaging to detect and study potentially salvageable penumbral tissue, the target for acute neuroprotection. Drug effects on penumbra lifespan studied serially, followed by assessment of behavioural outcome and infarct within in the same animal group, will increase the power to detect drug efficacy preclinically. Similar progress in detecting drug efficacy clinically will follow from patient recruitment into acute stroke trials based on evidence of remaining penumbra.

Item Type:Articles
Additional Information:The definitive version is available at
Glasgow Author(s) Enlighten ID:Macrae, Professor Mhairi
Authors: Macrae, I.M.
Subjects:R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:British Journal of Pharmacology
ISSN (Online):1476-5381
Published Online:26 September 2011
Copyright Holders:Copyright © 2011 The Author and The British Journal of Pharmacology
First Published:First published in British Journal of Pharmacology 164(4):1062-1078
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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