Department of Anesthesiology, Center for Shock, Trauma and Anesthesiology Research, School of Medicine, University of Maryland Baltimore, 685 West Baltimore street, MSTF 534, Baltimore, MD, 21201, USA,
Transl Stroke Res. 2013 Jun;4(3):343-50. doi: 10.1007/s12975-012-0236-z. Epub 2012 Dec 14.
Mouse models of global cerebral ischemia are essential tools to study the molecular mechanisms involved in ischemic brain damage. The availability of genetically engineered mice allows examination of the role of specific proteins in brain pathology processes. However, relative to rat models, mouse global brain ischemia models are technically more challenging to produce. It is important to emphasize that occlusion of two carotid arteries only is highly inefficient to produce consistent brain damage in mice. This is mainly due to high variability in their vascular anatomy. Several approaches were developed to achieve sufficient reduction of blood flow in the mouse brain that led to consistent ischemic brain damage. We describe here the mouse ischemic models most frequently utilized in research laboratories to test the effect of genetically manipulated proteins of interest on ischemic brain injury or to assess a drug effect on ischemia-induced brain damage. The most common approach used is the bilateral common carotid occlusion that is combined with either occlusion of a third artery or with concomitant reduction of mean arterial blood pressure. Furthermore, a four-vessel occlusion model can be used or even a cardiac arrest model that has been developed for mouse. All these models have specific problems, advantages, and clinical relevance. Thus, the feasibility of using a particular model depends on the goal of the study and the outcome parameters assessed. Overall, the mouse models are valuable since they allow the study of ischemia-induced molecular mechanisms utilizing transgenic animals and also evaluate the effect of new neuroprotective compounds.
鼠全脑缺血模型是研究缺血性脑损伤相关分子机制的重要工具。基因工程小鼠的可用性允许检查特定蛋白质在脑病理过程中的作用。然而，与大鼠模型相比，鼠全脑缺血模型在技术上更具挑战性。需要强调的是，仅仅阻塞两条颈内动脉对于在小鼠中产生一致的脑损伤效率非常低。这主要是由于它们的血管解剖结构高度可变。已经开发了几种方法来实现小鼠脑血流的充分减少，从而导致一致的缺血性脑损伤。我们在这里描述了在研究实验室中最常使用的鼠缺血模型，以测试感兴趣的基因操作蛋白对缺血性脑损伤的影响，或评估药物对缺血性脑损伤的影响。最常用的方法是双侧颈总动脉闭塞，同时伴有第三动脉阻塞或平均动脉血压同时降低。此外，还可以使用四血管闭塞模型，甚至可以为小鼠开发心脏骤停模型。所有这些模型都有特定的问题、优点和临床相关性。因此，使用特定模型的可行性取决于研究的目的和评估的结果参数。总体而言，鼠模型具有重要价值，因为它们允许利用转基因动物研究缺血诱导的分子机制，并评估新的神经保护化合物的效果。
