Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia
Procedural and strain-related variables significantly affect outcome in a murine model of focal cerebral ischemia
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DOI：
10.1097/00006123-199603000-00021
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发表时间：
1996-03-01
期刊：
影响因子：
4.8
通讯作者：
Pinsky, DJ
中科院分区：
文献类型：
--
作者：
Connolly, ES;Winfree, CJ;Pinsky, DJ
最近转基因小鼠的出现导致了大量描述特定基因产物对中风病理生理学影响的报告。虽然大鼠局灶性脑缺血模型已经得到了很好的描述，但对大脑中动脉闭塞的小鼠模型的描述很少，潜在的实验变异性的来源仍然不确定。我们假设，轻微的技术改进将在卒中小鼠模型中产生广泛不同的结果，控制手术和程序条件可能导致可重复的生理和解剖卒中结果。为了验证这一假设，我们建立了一种小鼠模型，可以通过闭塞大脑中动脉来实现永久性或短暂性局灶性脑缺血。这项研究详细描述了手术技术，并揭示了在转基因小鼠生产中常用的菌株之间的重要差异。除了应变相关的差异外，脑梗塞体积、神经预后和脑血流量似乎还受到缺血期和缺血期温度、小鼠大小和阻塞血管管腔的缝线大小的重要影响。当这些变量保持不变时，卒中结果有显著的一致性。这些数据强调了低温对中风的保护作用，并可能有助于标准化不同实验室的技术，为评估未来转基因动物研究的结果提供一个连贯的框架。
THE RECENT AVAILABILITY of transgenic mice has led to a burgeoning number of reports describing the effects of specific gene products on the pathophysiology of stroke. Although focal cerebral ischemia models in rats have been well described, descriptions of a murine model of middle cerebral artery occlusion are scant and sources of potential experimental variability remain undefined. We hypothesized that slight technical modifications would produce widely discrepant results in a murine model of stroke and that controlling surgical and procedural conditions could lead to reproducible physiological and anatomic stroke outcomes. To test this hypothesis, we established a murine model that would permit either permanent or transient focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery. This study provides a detailed description of the surgical technique and reveals important differences among strains commonly used in the production of transgenic mice. In addition to strain-related differences, infarct volume, neurological outcome, and cerebral blood flow appear to be importantly affected by temperature during the ischemic and postischemic periods, mouse size, and the size of the suture that obstructs the vascular lumen. When these variables were kept constant, there was remarkable uniformity of stroke outcome. These data emphasize the protective effects of hypothermia in stroke and might help to standardize techniques among different laboratories to provide a cohesive framework for evaluating the results of future studies in transgenic animals.