Animal models of ischemic stroke and their application in clinical research.
Animal models of ischemic stroke and their application in clinical research.
复制标题
DOI：
10.2147/dddt.s56071
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kleinschnitz C
中科院分区：
文献类型：
--
作者：
Fluri F;Schuhmann MK;Kleinschnitz C
本综述概述了最常用的啮齿动物脑卒中模型，并讨论了它们的优点和缺点。在一种动物模型中模拟人类脑卒中的所有方面是不可行的，因为人类缺血性脑卒中是一种具有复杂病理生理学的异质性疾病。大脑中动脉短暂性或永久性闭塞（MCAo）模型是最接近模拟人类缺血性脑卒中的模型之一。此外，该模型的特点是梗死灶可靠且重复性好。因此，MCAo模型已用于大多数涉及病理生理过程或神经保护剂的研究。另一种模型使用血栓栓塞凝块，因此更便于研究溶栓剂和溶栓后的病理生理过程。然而，由于多种原因，临床前脑卒中研究的转化成功率较低。一个因素可能是脑卒中模型的选择。人类永久性局灶性脑卒中的治疗反应性在发病后3小时内显著下降，而在及时再灌注的动物模型中，治疗窗口可达12小时，导致所研究药物的作用时间长得多。动物脑卒中模型的另一个主要问题是，研究大多在没有任何合并症的年轻动物中进行。这些模型与人类脑卒中不同，人类脑卒中尤其影响具有各种脑血管危险因素的老年人。选择最合适的脑卒中模型并优化临床前试验的研究设计可能会提高动物脑卒中模型的转化潜力。
This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.