A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta).
A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta).
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DOI：
10.1089/neu.2015.3956
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发表时间：
2016-03-01
影响因子：
4.2
通讯作者：
Beattie MS
中科院分区：
文献类型：
--
作者：
Salegio EA;Bresnahan JC;Sparrey CJ;Camisa W;Fischer J;Leasure J;Buckley J;Nout-Lomas YS;Rosenzweig ES;Moseanko R;Strand S;Hawbecker S;Lemoy MJ;Haefeli J;Ma X;Nielson JL;Edgerton VR;Ferguson AR;Tuszynski MH;Beattie MS
本文介绍了一种基于力学和计算机模拟的非人灵长类动物脊髓损伤（SCI）模型的建立。我们使用高度可控、无摩擦、电子驱动的致动器将啮齿动物模型扩大到更大的灵长类动物模型，以产生单侧C6-C7脊髓损伤。根据预设的影响参数，在9个NHP中产生了不同程度的功能恢复的分级挫伤病变。通过将撞击方案与每只动物的椎管、脊髓和脑脊液空间的大小相匹配，使用方案和术前磁共振成像（MRI）来优化结局的可预测性。术后MRI证实了病变位置，并提供了病变体积和扩散的信息，以与组织学测量进行比较。我们评估了影响参数，病变措施和行为结果之间的关系，并证实这些关系与我们以前的研究是一致的。除了提供多个单变量的结果指标外，我们还开发了一个描述多变量颈椎SCI综合征的综合结果指标。在较高范围的峰值力的影响产生了高度偏侧化和持久的缺陷，在多个措施的前肢和手的功能，而较低的能量的影响产生了早期的弱点，其次是实质性的恢复，但持久的赤字，在精细的数字控制（例如，钳抓）。该模型提供了一个临床相关系统，用于评价候选转化疗法的安全性和潜在疗效。
The development of a non-human primate (NHP) model of spinal cord injury (SCI) based on mechanical and computational modeling is described. We scaled up from a rodent model to a larger primate model using a highly controllable, friction-free, electronically-driven actuator to generate unilateral C6-C7 spinal cord injuries. Graded contusion lesions with varying degrees of functional recovery, depending upon pre-set impact parameters, were produced in nine NHPs. Protocols and pre-operative magnetic resonance imaging (MRI) were used to optimize the predictability of outcomes by matching impact protocols to the size of each animal's spinal canal, cord, and cerebrospinal fluid space. Post-operative MRI confirmed lesion placement and provided information on lesion volume and spread for comparison with histological measures. We evaluated the relationships between impact parameters, lesion measures, and behavioral outcomes, and confirmed that these relationships were consistent with our previous studies in the rat. In addition to providing multiple univariate outcome measures, we also developed an integrated outcome metric describing the multivariate cervical SCI syndrome. Impacts at the higher ranges of peak force produced highly lateralized and enduring deficits in multiple measures of forelimb and hand function, while lower energy impacts produced early weakness followed by substantial recovery but enduring deficits in fine digital control (e.g., pincer grasp). This model provides a clinically relevant system in which to evaluate the safety and, potentially, the efficacy of candidate translational therapies.