INSERM U1051, Rue Augustin Fliche, F-34095, Montpellier Cedex 5, France.
CHRU Montpellier, Gui de Chauliac Hospital, F-34095, Montpellier, France.
Neurotherapeutics. 2018 Jul;15(3):751-769. doi: 10.1007/s13311-017-0589-9.
Spinal cord injuries (SCI) lead to major disabilities affecting > 2.5 million people worldwide. Major shortcomings in clinical translation result from multiple factors, including species differences, development of moderately predictive animal models, and differences in methodologies between preclinical and clinical studies. To overcome these obstacles, we first conducted a comparative neuroanatomical analysis of the spinal cord between mice, Microcebus murinus (a nonhuman primate), and humans. Next, we developed and characterized a new model of lateral spinal cord hemisection in M. murinus. Over a 3-month period after SCI, we carried out a detailed, longitudinal, behavioral follow-up associated with in vivo magnetic resonance imaging (H-MRI) monitoring. Then, we compared lesion extension and tissue alteration using 3 methods: in vivo H-MRI, ex vivo H-MRI, and classical histology. The general organization and glial cell distribution/morphology in the spinal cord of M. murinus closely resembles that of humans. Animals assessed at different stages following lateral hemisection of the spinal cord presented specific motor deficits and spinal cord tissue alterations. We also found a close correlation between H-MRI signal and microglia reactivity and/or associated post-trauma phenomena. Spinal cord hemisection in M. murinus provides a reliable new nonhuman primate model that can be used to promote translational research on SCI and represents a novel and more affordable alternative to larger primates.
脊髓损伤 (SCI) 导致全球超过 250 万人出现重大残疾。临床转化的主要缺点源于多种因素，包括物种差异、中度预测性动物模型的开发以及临床前和临床研究方法之间的差异。为了克服这些障碍，我们首先对小鼠、Microcebus murinus（一种非人类灵长类动物）和人类的脊髓进行了比较神经解剖学分析。接下来，我们在 M. murinus 中开发并表征了一种新的脊髓侧半切模型。在 SCI 后 3 个月的时间里，我们进行了详细的、纵向的、行为学随访，并结合体内磁共振成像（H-MRI）监测。然后，我们使用 3 种方法比较损伤扩展和组织改变：体内 H-MRI、离体 H-MRI 和经典组织学。M. murinus 脊髓的一般组织和神经胶质细胞分布/形态与人类非常相似。在脊髓侧半切后不同阶段评估的动物表现出特定的运动缺陷和脊髓组织改变。我们还发现 H-MRI 信号与小胶质细胞反应性和/或相关创伤后现象之间存在密切相关性。M. murinus 的脊髓半切提供了一种可靠的新型非人类灵长类动物模型，可用于促进 SCI 的转化研究，并且代表了一种新颖且更经济实惠的替代较大灵长类动物的选择。
