1 Indiana Spinal Cord and Brain Injury Research Group, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana.
2 Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
J Neurotrauma. 2019 Feb 1;36(3):460-468. doi: 10.1089/neu.2018.5756. Epub 2018 Aug 13.
Mouse models are unique for studying molecular mechanisms of neurotrauma because of the availability of various genetic modified mouse lines. For spinal cord injury (SCI) research, producing an accurate injury is essential, but it is challenging because of the small size of the mouse cord and the inconsistency of injury production. The Louisville Injury System Apparatus (LISA) impactor has been shown to produce precise contusive SCI in adult rats. Here, we examined whether the LISA impactor could be used to create accurate and graded contusive SCIs in mice. Adult C57BL/6 mice received a T10 laminectomy followed by 0.2, 0.5, and 0.8 mm displacement injuries, guided by a laser, from the dorsal surface of the spinal cord using the LISA impactor. Basso Mouse Scale (BMS), grid-walking, TreadScan, and Hargreaves analyses were performed for up to 6 weeks post-injury. All mice were euthanized at the 7th week, and the spinal cords were collected for histological analysis. Our results showed that the LISA impactor produced accurate and consistent contusive SCIs corresponding to mild, moderate, and severe injuries to the cord. The degree of injury severities could be readily determined by the BMS locomotor, grid-walking, and TreadScan gait assessments. The cutaneous hyperalgesia threshold was also significantly increased as the injury severity increased. The terminal lesion area and the spared white matter of the injury epicenter were strongly correlated with the injury severities. We conclude that the LISA device, guided by a laser, can produce reliable graded contusive SCIs in mice, resulting in severity-dependent behavioral and histopathological deficits.
小鼠模型在研究神经创伤的分子机制方面具有独特性,因为可以获得各种基因修饰的小鼠品系。对于脊髓损伤(SCI)研究,产生准确的损伤至关重要,但由于小鼠脊髓的体积小和损伤产生的不一致性,这具有挑战性。路易维尔损伤系统仪器(LISA)撞击器已被证明可在成年大鼠中产生精确的挫伤性 SCI。在这里,我们研究了 LISA 撞击器是否可用于在小鼠中创建准确且分级的挫伤性 SCI。成年 C57BL/6 小鼠接受 T10 椎板切除术,然后使用 LISA 撞击器从脊髓背表面通过激光引导进行 0.2、0.5 和 0.8mm 位移损伤。在损伤后最多 6 周进行 Basso 小鼠量表(BMS)、网格行走、TreadScan 和 Hargreaves 分析。所有小鼠在第 7 周处死,并收集脊髓进行组织学分析。我们的结果表明,LISA 撞击器产生了准确且一致的挫伤性 SCI,与脊髓的轻度、中度和重度损伤相对应。BMS 运动、网格行走和 TreadScan 步态评估可轻松确定损伤严重程度。随着损伤严重程度的增加,皮肤痛觉过敏阈值也显著增加。终末病变面积和损伤中心周围的白质保留量与损伤严重程度密切相关。我们得出结论,激光引导的 LISA 设备可在小鼠中产生可靠的分级挫伤性 SCI,导致与严重程度相关的行为和组织病理学缺陷。