Ingberg Edvin, Dock Hua, Theodorsson Elvar, Theodorsson Annette, Ström Jakob O
Division of Microbiology and Molecular Medicine, Department of Clinical and Experimental Medicine, Linköping University, Department of Clinical Chemistry, Center for Diagnostics, Region Östergötland, Sweden.
Division of Neuro and Inflammation Science, Department of Clinical and Experimental Medicine, Linköping University, Department of Neurosurgery, Anaesthetics, Operations and Specialty Surgery Center, Region Östergötland, Sweden.
Sci Rep. 2016 Feb 15;6:21086. doi: 10.1038/srep21086.
Although hundreds of promising substances have been tested in clinical trials, thrombolysis currently remains the only specific pharmacological treatment for ischemic stroke. Poor quality, e.g. low statistical power, in the preclinical studies has been suggested to play an important role in these failures. Therefore, it would be attractive to use animal models optimized to minimize unnecessary mortality and outcome variability, or at least to be able to power studies more exactly by predicting variability and mortality given a certain experimental setup. The possible combinations of methodological parameters are innumerous, and an experimental comparison of them all is therefore not feasible. As an alternative approach, we extracted data from 334 experimental mouse stroke articles and, using a hypothesis-driven meta-analysis, investigated the method parameters' impact on infarct size variability and mortality. The use of Swiss and C57BL6 mice as well as permanent occlusion of the middle cerebral artery rendered the lowest variability of the infarct size while the emboli methods increased variability. The use of Swiss mice increased mortality. Our study offers guidance for researchers striving to optimize mouse stroke models.
尽管已有数百种有前景的物质在临床试验中进行了测试，但溶栓目前仍然是缺血性中风唯一的特异性药物治疗方法。临床前研究质量不佳，例如统计效力低，被认为在这些失败中起重要作用。因此，使用经过优化以尽量减少不必要的死亡率和结果变异性的动物模型，或者至少能够通过预测给定特定实验设置下的变异性和死亡率来更准确地进行研究，将是很有吸引力的。方法学参数的可能组合数不胜数，因此对它们全部进行实验比较是不可行的。作为一种替代方法，我们从334篇实验性小鼠中风文章中提取数据，并使用假设驱动的荟萃分析，研究了方法学参数对梗死灶大小变异性和死亡率的影响。使用瑞士小鼠和C57BL6小鼠以及大脑中动脉永久性闭塞导致梗死灶大小的变异性最低，而栓塞方法则增加了变异性。使用瑞士小鼠会增加死亡率。我们的研究为致力于优化小鼠中风模型的研究人员提供了指导。
