Plemel Jason R, Duncan Greg, Chen Kai-Wei K, Shannon Casey, Park Sophia, Sparling Joseph S, Tetzlaff Wolfram
ICORD (International Collaboration on Repair Discoveries), University of British Columbia, Vancouver, British Columbia, Canada.
J Neurotrauma. 2008 Apr;25(4):350-70. doi: 10.1089/neu.2007.0426.
Given the rising availability and use of genetically modified animals in basic science research, it has become increasingly important to develop clinically relevant models for spinal cord injury (SCI) for use in mice. We developed a graded forceps crush model of SCI in mice that uses three different forceps with spacers of 0.25, 0.4, and 0.55 mm, to produce severe, moderate, and mild injuries, respectively. Briefly, each mouse was subjected to laminectomy of T5-T7, 15-second spinal cord crush using one of those forceps, behavioral assessments, and post-mortem neuroanatomical analyses. There were significant differences among the three injury severity groups on behavioral measures (Basso Mouse Score, footprint, and ladder analyses), demonstrating an increase in neurological deficits for groups with greater injury severity. Quantitative analysis of the lesion demonstrated that as injury severity increased, lesion size and GFAP negative area increased, and spared tissue, spinal cord cross-sectional area, spared grey matter and spared white matter decreased. These measures strongly correlated with the behavioral outcomes. Similar to other studies of SCI in mice, we report a dense laminin and fibronectin positive extracellular matrix in the lesion sites of injured mice, but unlike those previous studies, we also report the presence of numerous p75 positive Schwann cells in and around the lesion epicenter. These results provide evidence that the graded forceps crush model is an attractive alternative for the study of SCI and related therapeutic interventions. Because of its demonstrated consistency, ease of use, low cost, and clinical relevance, this graded forceps crush is an attractive alternative to the other mouse models of SCI currently available.
鉴于转基因动物在基础科学研究中的可用性和使用日益增加,开发适用于小鼠的临床相关脊髓损伤(SCI)模型变得越来越重要。我们开发了一种小鼠SCI分级镊子挤压模型,该模型使用三种不同的带间隔物的镊子,间隔物分别为0.25、0.4和0.55毫米,分别产生重度、中度和轻度损伤。简要地说,每只小鼠接受T5 - T7椎板切除术,使用其中一种镊子进行15秒的脊髓挤压,进行行为评估和死后神经解剖分析。在行为测量(Basso小鼠评分、足迹和阶梯分析)方面,三个损伤严重程度组之间存在显著差异,表明损伤严重程度较高的组神经功能缺损增加。病变的定量分析表明,随着损伤严重程度的增加,病变大小和GFAP阴性面积增加, spared组织、脊髓横截面积、 spared灰质和 spared白质减少。这些测量结果与行为结果密切相关。与其他小鼠SCI研究类似,我们报告了受伤小鼠病变部位有密集的层粘连蛋白和纤连蛋白阳性细胞外基质,但与之前的那些研究不同,我们还报告了病变中心及其周围存在大量p75阳性雪旺细胞。这些结果提供了证据,表明分级镊子挤压模型是研究SCI和相关治疗干预的有吸引力的替代方法。由于其已证明的一致性、易用性、低成本和临床相关性,这种分级镊子挤压模型是目前可用的其他小鼠SCI模型的有吸引力的替代方法。