Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Center for Neurotrauma, Neurodegeneration & Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania.
Neurosurgery. 2020 Sep 15;87(4):833-846. doi: 10.1093/neuros/nyaa106.
Millions of Americans experience residual deficits from traumatic peripheral nerve injury (PNI). Despite advancements in surgical technique, repair typically results in poor functional outcomes due to prolonged periods of denervation resulting from long regenerative distances coupled with slow rates of axonal regeneration. Novel surgical solutions require valid preclinical models that adequately replicate the key challenges of clinical PNI.
To develop a preclinical model of PNI in swine that addresses 2 challenging, clinically relevant PNI scenarios: long segmental defects (≥5 cm) and ultra-long regenerative distances (20-27 cm). Thus, we aim to demonstrate that a porcine model of major PNI is suitable as a potential framework to evaluate novel regenerative strategies prior to clinical deployment.
A 5-cm-long common peroneal nerve or deep peroneal nerve injury was repaired using a saphenous nerve or sural nerve autograft, respectively. Histological and electrophysiological assessments were performed at 9 to 12 mo post repair to evaluate nerve regeneration and functional recovery. Relevant anatomy, surgical approach, and functional/histological outcomes were characterized for both repair techniques.
Axons regenerated across the repair zone and were identified in the distal stump. Electrophysiological recordings confirmed these findings and suggested regenerating axons reinnervated target muscles.
The models presented herein provide opportunities to investigate peripheral nerve regeneration using different nerves tailored for specific mechanisms of interest, such as nerve modality (motor, sensory, and mixed fiber composition), injury length (short/long gap), and total regenerative distance (proximal/distal injury).
数以百万计的美国人经历外伤性周围神经损伤 (PNI) 的残留缺陷。尽管手术技术取得了进步，但由于长时间的去神经支配导致再生距离长，再加上轴突再生速度缓慢，修复通常会导致功能不良的结果。新的手术解决方案需要有效的临床前模型，该模型充分复制了临床 PNI 的关键挑战。
开发一种在猪中的 PNI 临床前模型，该模型解决了 2 个具有挑战性的、与临床相关的 PNI 场景：长节段缺损（≥5 cm）和超长再生距离（20-27 cm）。因此，我们旨在证明主要 PNI 的猪模型适合作为在临床部署之前评估新型再生策略的潜在框架。
使用隐神经或腓肠神经自体移植物修复 5cm 长的腓总神经或腓深神经损伤。在修复后 9 至 12 个月进行组织学和电生理学评估，以评估神经再生和功能恢复情况。对两种修复技术的相关解剖结构、手术方法和功能/组织学结果进行了描述。
轴突在修复区再生，并在远端残端中被识别。电生理记录证实了这些发现，并表明再生轴突重新支配了目标肌肉。
本文提出的模型为使用不同的神经来研究周围神经再生提供了机会，这些神经可针对特定的感兴趣机制进行定制，例如神经模式（运动、感觉和混合纤维组成）、损伤长度（短/长间隙）和总再生距离（近端/远端损伤）。
