Animal models of ischaemic stroke and characterisation of the ischaemic penumbra

McCabe, C. , Arroja, M. M., Reid, E. and Macrae, I. M. (2018) Animal models of ischaemic stroke and characterisation of the ischaemic penumbra. Neuropharmacology, 134(Pt. B), pp. 169-177. (doi: 10.1016/j.neuropharm.2017.09.022) (PMID:28923277)

Abstract

Over the past forty years, animal models of focal cerebral ischaemia have allowed us to identify the critical cerebral blood flow thresholds responsible for irreversible cell death, electrical failure, inhibition of protein synthesis, energy depletion and thereby the lifespan of the potentially salvageable penumbra. They have allowed us to understand the intricate biochemical and molecular mechanisms within the ‘ischaemic cascade’ that initiate cell death in the first minutes, hours and days following stroke. Models of permanent, transient middle cerebral artery occlusion and embolic stroke have been developed each with advantages and limitations when trying to model the complex heterogeneous nature of stroke in humans. Yet despite these advances in understanding the pathophysiological mechanisms of stroke-induced cell death with numerous targets identified and drugs tested, a lack of translation to the clinic has hampered pre-clinical stroke research. With recent positive clinical trials of endovascular thrombectomy in acute ischaemic stroke the stroke community has been reinvigorated, opening up the potential for future translation of adjunctive treatments that can be given alongside thrombectomy/thrombolysis. This review discusses the major animal models of focal cerebral ischaemia highlighting their advantages and limitations. Acute imaging is crucial in longitudinal pre-clinical stroke studies in order to identify the influence of acute therapies on tissue salvage over time. Therefore, the methods of identifying potentially salvageable ischaemic penumbra are discussed.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Macrae, Professor Mhairi and Arroja, Mariana Moreira Coutinho and Reid, Dr Emma and McCabe, Dr Chris
• Authors: McCabe, C., Arroja, M. M., Reid, E., and Macrae, I. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Neuropharmacology
• Publisher: Elsevier
• ISSN: 0028-3908
• ISSN (Online): 1873-7064
• Published Online: 18 September 2017
• Copyright Holders: Copyright © 2017 Elsevier Ltd.
• First Published: First published in Neuropharmacology 134(pt. B):169-177
• Publisher Policy: Reproduced in accordance with the publisher copyright policy