Trotman-Lucas Melissa, Kelly Michael E, Janus Justyna, Fern Robert, Gibson Claire L
Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester LE1 9HN, UK.
Preclinical Imaging Facility, Core Biotechnology Services, University of Leicester, Leicester LE1 9HN, UK.
Dis Model Mech. 2017 Jul 1;10(7):931-938. doi: 10.1242/dmm.029108. Epub 2017 May 26.
Animal models are essential for understanding the pathology of stroke and investigating potential treatments. However, stroke models are associated, particularly in mice, with high variability in lesion volume. We investigated whether a surgical refinement where reperfusion is not reliant on the Circle of Willis reduced outcome variability. Mice underwent 60 min of transient middle cerebral artery occlusion avoiding ligation of the external carotid artery. During reperfusion, the common carotid artery was either ligated (standard approach), or it was repaired to allow re-establishment of blood flow through the common carotid artery. All mice underwent MRI scanning for assessment of infarct volume, apparent diffusion coefficient and fractional anisotropy, along with terminal assessment of infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Repairing the common carotid artery following middle cerebral artery occlusion enhanced reperfusion (<0.01) and reduced the variability seen in both total (histological analysis, =0.008; T2-weighted MRI, =0.015) and core (diffusion tensor MRI, =0.043) lesion volume. Avoiding external carotid artery ligation may improve animal wellbeing, through reduced weight loss, while using an alternative surgical approach that enabled reperfusion through the common carotid artery decreased the variability in lesion volume seen within groups.
动物模型对于理解中风的病理以及研究潜在治疗方法至关重要。然而,中风模型,尤其是在小鼠中,与病变体积的高度变异性相关。我们研究了一种手术改进方法,即再灌注不依赖于 Willis 环,是否能降低结果的变异性。小鼠接受 60 分钟的短暂大脑中动脉闭塞,避免结扎颈外动脉。在再灌注期间,颈总动脉要么被结扎(标准方法),要么进行修复以允许通过颈总动脉重新建立血流。所有小鼠都接受了 MRI 扫描,以评估梗死体积、表观扩散系数和分数各向异性,并通过 2,3,5 - 三苯基四氮唑氯化物(TTC)染色对梗死体积进行终末评估。大脑中动脉闭塞后修复颈总动脉可增强再灌注(<0.01),并降低总病变体积(组织学分析,=0.008;T2 加权 MRI,=0.015)和核心病变体积(扩散张量 MRI,=0.043)中观察到的变异性。避免结扎颈外动脉可能通过减少体重减轻来改善动物健康状况,同时使用一种能够通过颈总动脉实现再灌注的替代手术方法可降低组内观察到的病变体积变异性。