Department of Physical Therapy, University of Alberta, Edmonton, Alberta, Canada.
J Cereb Blood Flow Metab. 2012 Apr;32(4):612-27. doi: 10.1038/jcbfm.2012.8. Epub 2012 Feb 1.
The likelihood of translating therapeutic interventions for stroke rests on the quality of preclinical science. Given the limited success of putative treatments for ischemic stroke and the reasons put forth to explain it, we sought to determine whether such problems hamper progress for intracerebral hemorrhage (ICH). Approximately 10% to 20% of strokes result from an ICH, which results in considerable disability and high mortality. Several animal models reproduce ICH and its underlying pathophysiology, and these models have been widely used to evaluate treatments. As yet, however, none has successfully translated. In this review, we focus on rodent models of ICH, highlighting differences among them (e.g., pathophysiology), issues with experimental design and analysis, and choice of end points. A Pub Med search for experimental ICH (years: 2007 to 31 July 2011) found 121 papers. Of these, 84% tested neuroprotectants, 11% tested stem cell therapies, and 5% tested rehabilitation therapies. We reviewed these to examine study quality (e.g., use of blinding procedures) and choice of end points (e.g., behavioral testing). Not surprisingly, the problems that have plagued the ischemia field are also prevalent in ICH literature. Based on these data, several recommendations are put forth to facilitate progress in identifying effective treatments for ICH.
将治疗干预措施转化为中风的可能性取决于临床前科学的质量。鉴于缺血性中风的潜在治疗方法的有限成功,以及提出的解释这些方法的原因,我们试图确定这些问题是否阻碍了脑出血 (ICH) 的进展。大约 10%至 20%的中风是由 ICH 引起的,这会导致相当大的残疾和高死亡率。有几种动物模型可以模拟 ICH 及其潜在的病理生理学,这些模型已被广泛用于评估治疗方法。然而,到目前为止,还没有一种方法成功转化。在这篇综述中,我们专注于 ICH 的啮齿动物模型,重点介绍它们之间的差异(例如,病理生理学)、实验设计和分析中的问题,以及终点的选择。在实验性 ICH 方面,我们通过 Pub Med 进行了搜索(年份:2007 年至 2011 年 7 月 31 日),共发现 121 篇论文。其中,84%的论文测试了神经保护剂,11%的论文测试了干细胞疗法,5%的论文测试了康复疗法。我们对这些论文进行了回顾,以检查研究质量(例如,是否使用了盲法程序)和终点的选择(例如,行为测试)。毫不奇怪,困扰缺血性中风领域的问题在 ICH 文献中也很普遍。基于这些数据,我们提出了一些建议,以促进确定有效的 ICH 治疗方法的进展。