A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research
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REVIEW ARTICLE
A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research Sarah E. Withers 1 & Adrian R. Parry-Jones 2,3 & Stuart M. Allan 1 & Paul R. Kasher 1 Received: 15 May 2020 / Revised: 18 June 2020 / Accepted: 23 June 2020 # The Author(s) 2020
Abstract Apart from acute and chronic blood pressure lowering, we have no specific medications to prevent intracerebral haemorrhage (ICH) or improve outcomes once bleeding has occurred. One reason for this may be related to particular limitations associated with the current pre-clinical models of ICH, leading to a failure to translate into the clinic. It would seem that a breakdown in the ‘drug development pipeline’ currently exists for translational ICH research which needs to be urgently addressed. Here, we review the most commonly used pre-clinical models of ICH and discuss their advantages and disadvantages in the context of translational studies. We propose that to increase our chances of successfully identifying new therapeutics for ICH, a bidirectional, 2- or 3-pronged approach using more than one model species/system could be useful for confirming key preclinical observations. Furthermore, we highlight that post-mortem/ex-vivo ICH patient material is a precious and underused resource which could play an essential role in the verification of experimental results prior to consideration for further clinical investigation. Embracing multidisciplinary collaboration between pre-clinical and clinical ICH research groups will be essential to ensure the success of this type of approach in the future. Keywords Pre-clinical . Intracerebral haemorrhage . Disease models . Drug discovery
Introduction Stroke is the second highest cause of death worldwide, surpassed only by ischaemic heart disease [1]. The most devastating sub-type of stroke, intracerebral haemorrhage (ICH), accounts for 10–20% of all strokes in high-income countries, whilst incidences increase in central and East Asia and subSaharan Africa [2]. ICH has a mortality rate of 40% at 1month post-ictus, coupled with a higher loss of disability * Paul R. Kasher [email protected] 1
Division of Neuroscience and Experimental Psychology, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK
2
Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Oxford Road, Manchester M13 9PT, UK
3
Manchester Centre for Clinical Neurosciences, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, Stott Lane, Salford M6 8HD, UK
adjusted life years, exceeding that of ischaemic stroke despite lower prevalence [1, 3]. Knowledge of the molecular pathophysiology surrounding haemorrhagic stroke has vastly increased in recent years, with a plethora of reviews describing the primary and secondary injury phases [4–9]. Key modifiable ris
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