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.
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.
Transl Stroke Res. 2020 Dec;11(6):1229-1242. doi: 10.1007/s12975-020-00830-z. Epub 2020 Jul 7.
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 bi-directional, 2- or 3-pronged approach using more than one model species/system could be useful for confirming key pre-clinical 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.
除了急性和慢性降压之外,我们没有专门的药物可以预防脑出血 (ICH) 或在出血发生后改善预后。造成这种情况的一个原因可能与当前 ICH 临床前模型的特定局限性有关,导致无法转化为临床应用。目前,转化性 ICH 研究似乎存在“药物开发管道”的崩溃,这需要紧急解决。在这里,我们回顾了最常用的 ICH 临床前模型,并讨论了它们在转化研究中的优缺点。我们提出,为了增加成功确定 ICH 新疗法的机会,使用一种以上的模型物种/系统的双向、2 或 3 管齐下的方法可能有助于确认关键的临床前观察结果。此外,我们强调指出,死后/体外 ICH 患者材料是一种宝贵但未被充分利用的资源,它可以在考虑进一步临床研究之前,在验证实验结果方面发挥重要作用。接受临床前和临床 ICH 研究小组之间的多学科合作将是确保这种方法未来取得成功的关键。