一种新型的外伤性胸段脊髓损伤猪模型。
A novel porcine model of traumatic thoracic spinal cord injury.
机构信息
International Collaboration on Repair Discoveries, University of British Columbia, Vancouver, British Columbia, Canada .
出版信息
J Neurotrauma. 2013 Feb 1;30(3):142-59. doi: 10.1089/neu.2012.2386. Epub 2013 Jan 14.
Spinal cord injury (SCI) researchers have predominately utilized rodents and mice for in vivo SCI modeling and experimentation. From these small animal models have come many insights into the biology of SCI, and a growing number of novel treatments that promote behavioral recovery. It has, however, been difficult to demonstrate the efficacy of such treatments in human clinical trials. A large animal SCI model that is an intermediary between rodent and human SCI may be a valuable translational research resource for pre-clinically evaluating novel therapies, prior to embarking upon lengthy and expensive clinical trials. Here, we describe the development of such a large animal model. A thoracic spinal cord injury at T10/11 was induced in Yucatan miniature pigs (20-25 kg) using a weight drop device. Varying degrees of injury severity were induced by altering the height of the weight drop (5, 10, 20, 30, 40, and 50 cm). Behavioral recovery over 12 weeks was measured using a newly developed Porcine Thoracic Injury Behavior Scale (PTIBS). This scale distinguished locomotor recovery among animals of different injury severities, with strong intra-observer and inter-observer reliability. Histological analysis of the spinal cords 12 weeks post-injury revealed that animals with the more biomechanically severe injuries had less spared white matter and gray matter and less neurofilament immunoreactivity. Additionally, the PTIBS scores correlated strongly with the extent of tissue sparing through the epicenter of injury. This large animal model of SCI may represent a useful intermediary in the testing of novel pharmacological treatments and cell transplantation strategies.
脊髓损伤 (SCI) 研究人员主要利用啮齿动物和小鼠进行体内 SCI 建模和实验。从小鼠动物模型中,我们深入了解了 SCI 的生物学,并开发出越来越多促进行为恢复的新型治疗方法。然而,在人体临床试验中很难证明这些治疗方法的疗效。一种介于啮齿动物和人类 SCI 之间的大型动物 SCI 模型可能是一种有价值的转化研究资源,可用于在进行耗时且昂贵的临床试验之前,对新型疗法进行临床前评估。在这里,我们描述了这种大型动物模型的开发。使用重物坠落装置在尤卡坦微型猪(20-25 公斤)的 T10/11 胸椎诱导脊髓损伤。通过改变重物坠落的高度(5、10、20、30、40 和 50 厘米),可诱导不同严重程度的损伤。使用新开发的猪胸椎损伤行为量表 (PTIBS) 测量 12 周内的行为恢复情况。该量表可区分不同损伤严重程度动物的运动恢复情况,具有较强的观察者内和观察者间可靠性。损伤后 12 周的脊髓组织学分析表明,生物力学损伤更严重的动物保留的白质和灰质更少,神经丝免疫反应性更低。此外,PTIBS 评分与损伤中心的组织保留程度密切相关。这种新型 SCI 动物模型可能代表了测试新型药物治疗和细胞移植策略的有用中间物。