Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Medical Sciences Division, University of Oxford, Oxford, UK.
Brain. 2017 Aug 1;140(8):2079-2092. doi: 10.1093/brain/awx126.
Acute ischaemic stroke accounts for 6.5 million deaths per year, and by 2030 will result in the annual loss of over 200 million disability-adjusted life years globally. There have been considerable recent advances in the gold standard of acute ischaemic stroke treatment, some aspects of which-aspirin to prevent recurrence, and treating patients in specialized stroke wards-are widely applicable. Recanalization of the occluded artery through thrombolysis and/or endovascular thrombectomy is restricted to only a small proportion of patients, due to contra-indications and the costs associated with establishing the infrastructure to deliver these treatments. The use of neuroprotective agents in stroke has been a notable failure of translation from medical research into clinical practice. Yet, with the advent of endovascular thrombectomy and the ability to investigate patients in much greater detail through advanced imaging modalities, neuroprotective agents can and should be re-examined as adjunct therapies to recanalization. In parallel, this requires appropriate planning on behalf of the preclinical stroke research community: there is a need to reinvestigate these therapies in a more collaborative manner, to enhance reproducibility through reduced attrition, improved reporting, and adopting an approach to target validation that more closely mimics clinical trials. This review will describe some of the novel strategies being used in stroke research, and focus on a few key examples of neuroprotective agents that are showing newfound promise in preclinical models of stroke therapy. Our primary aim is to give an overview of some of the challenges faced by preclinical stroke research, and suggest potential ways to improve translational success.
急性缺血性脑卒中每年导致 650 万人死亡,到 2030 年,将导致每年全球超过 2 亿残疾调整生命年的损失。急性缺血性脑卒中治疗的金标准最近取得了相当大的进展,其中一些方面——阿司匹林预防复发和在专门的脑卒中病房治疗患者——具有广泛的适用性。由于禁忌症和建立提供这些治疗所需基础设施的相关成本,只有一小部分患者可以通过溶栓和/或血管内血栓切除术使闭塞的动脉再通。神经保护剂在脑卒中的应用是医学研究转化为临床实践的一个显著失败。然而,随着血管内血栓切除术的出现,以及通过先进的成像方式更详细地研究患者的能力,神经保护剂可以而且应该重新作为再通的辅助治疗进行检查。与此同时,这需要临床前脑卒中研究界代表的适当规划:有必要以更协作的方式重新研究这些疗法,通过减少损耗、改进报告以及采用更接近临床试验的方法来验证目标,从而提高可重复性。这篇综述将描述脑卒中研究中使用的一些新策略,并重点介绍一些神经保护剂的关键例子,这些例子在脑卒中治疗的临床前模型中显示出了新的希望。我们的主要目的是概述临床前脑卒中研究面临的一些挑战,并提出一些潜在的方法来提高转化的成功率。