1 The Miami Project to Cure Paralysis, University of Miami, Miller School of Medicine, Miami, Florida.
2 Department of Radiation Oncology, University of Miami, Miller School of Medicine, Miami, Florida.
J Neurotrauma. 2019 May 1;36(9):1399-1415. doi: 10.1089/neu.2018.6087. Epub 2018 Nov 20.
Neuroimaging facilitates the translation of animal pre-clinical research to human application. The large porcine spinal cord is useful for testing invasive interventions. Ideally, the safety and efficacy of a delayed intervention is tested in pigs that have recovered sufficiently after spinal cord injury (SCI) to allow either deterioration or improvement of function to be detected. We set out to create moderate severity T9 injuries in Yucatan minipigs by conducting a bridging study adapting methods previously developed in infant piglets. The injury severity was varied according to two pneumatic impactor parameters: the piston compression depth into tissue or the velocity. To stratify locomotor recovery, a 10-point scale used in prior piglet studies was redefined through longitudinal observations of spontaneous recovery. Using hindlimb body weight support to discriminate injury severity, we found that end-point recovery was strongly bimodal to either non-weight-bearing plegia with reciprocating leg movements (<5/10) or recovery of weight bearing that improved toward a ceiling effect (≥ 8/10). No intermediate recovery animals were observed at 2 months post-injury. The ability of intra-operative ultrasound and acute magnetic resonance imaging (MRI) to provide immediate predictive feedback regarding tissue and vascular changes following SCI was assessed. There was an inverse association between locomotor outcome and early gray matter hemorrhage on MRI and ultrasound. Epicenter blood flow following contusion predicted recovery or non-recovery of weight-bearing. The depth of the dorsal cerebrospinal fluid space, which varied between animals, influenced injury severity and confounded the results in this fixed-stroke paradigm.
神经影像学促进了动物临床前研究向人类应用的转化。大型猪的脊髓非常适合用于测试侵入性干预措施。理想情况下，在脊髓损伤 (SCI) 后恢复得足够好的猪身上测试延迟干预的安全性和有效性，以便能够检测到功能的恶化或改善。我们通过适应以前在仔猪中开发的方法，开展了一项桥接研究，旨在创建 Yucatan 小型猪的中度严重 T9 损伤。损伤严重程度根据两个气动冲击器参数而变化：活塞进入组织的压缩深度或速度。为了对运动功能恢复进行分层，通过对自发性恢复的纵向观察，重新定义了以前在仔猪研究中使用的 10 分制评分标准。使用后肢体重支持来区分损伤严重程度，我们发现，终点恢复要么是不承重截瘫伴腿部往复运动（<5/10），要么是承重能力改善到接近上限（≥8/10），呈强烈双峰模式。在损伤后 2 个月时，未观察到中间恢复的动物。评估了术中超声和急性磁共振成像 (MRI) 在 SCI 后提供关于组织和血管变化的即时预测反馈的能力。运动功能恢复与 MRI 和超声上的早期灰质出血之间存在负相关。挫伤后的中心血流预测了承重能力的恢复或不恢复。背侧脑脊液空间的深度在动物之间有所不同，影响了损伤严重程度，并使这种固定性中风模型的结果复杂化。
