Department of Psychology, University of Alberta, Edmonton, Alberta, Canada.
Stroke. 2010 Oct;41(10 Suppl):S95-8. doi: 10.1161/STROKEAHA.110.594457.
The collagenase and whole blood intracerebral hemorrhage (ICH) models are widely used to identify mechanisms of injury and to evaluate treatments. Despite preclinical successes, to date, no treatment tested in phase III clinical trials has benefited ICH patients. These failures call into question the predictive value of current ICH models. By highlighting differences between these common rodent models of ICH, we sought to help investigators choose the more appropriate model for their study and to encourage the use of both whenever possible. For instance, we previously reported substantial differences in the bleeding profile, progression of cell death, and functional outcome between these models. These and other differences influence the efficacy and mechanisms of action of various treatment modalities. Thus, in this review, we also summarize neuroprotective and rehabilitation findings in each model. We conclude that differences between ICH models along with our current inability to identify the more clinically predictive model necessitate that preclinical assessments should normally be done in both. Such an approach, coupled with better assessment practices, will likely improve chances of future clinical success.
胶原酶和全血脑出血 (ICH) 模型被广泛用于确定损伤机制和评估治疗方法。尽管在临床前研究中取得了成功,但迄今为止,在 III 期临床试验中测试的没有一种治疗方法对 ICH 患者有益。这些失败对当前 ICH 模型的预测价值提出了质疑。通过强调这些常见的脑出血啮齿动物模型之间的差异,我们希望帮助研究人员为他们的研究选择更合适的模型,并鼓励尽可能同时使用这两种模型。例如,我们之前报道了这些模型在出血情况、细胞死亡进展和功能结果方面存在显著差异。这些和其他差异影响各种治疗方法的疗效和作用机制。因此,在这篇综述中,我们还总结了每个模型中的神经保护和康复发现。我们得出结论,ICH 模型之间的差异以及我们目前无法确定更具临床预测性的模型,这意味着通常需要在两个模型中进行临床前评估。这种方法结合更好的评估实践,可能会提高未来临床成功的机会。