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A Porcine Model of Peripheral Nerve Injury Enabling Ultra-Long Regenerative Distances: Surgical Approach, Recovery Kinetics, and Clinical Relevance
Neurosurgery ( IF 3.9 ) Pub Date : 2020-05-11 , DOI: 10.1093/neuros/nyaa106
Justin C Burrell 1, 2, 3 , Kevin D Browne 1, 2 , John L Dutton 1 , Franco A Laimo 1, 2 , Suradip Das 1, 2 , Daniel P Brown 1, 2 , Sanford Roberts 1, 2 , Dmitriy Petrov 1, 2 , Zarina Ali 1 , Harry C Ledebur 4 , Joseph M Rosen 5 , Hilton M Kaplan 6 , John A Wolf 1, 2 , Douglas H Smith 1, 4 , H Isaac Chen 1, 2 , D Kacy Cullen 1, 2, 3, 4
Affiliation  

BACKGROUND 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. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION 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).

中文翻译:

可实现超长再生距离的外周神经损伤猪模型:手术方法、恢复动力学和临床相关性

背景技术数百万美国人经历外伤性周围神经损伤(PNI)的残余缺陷。尽管手术技术有所进步,但由于再生距离长以及轴突再生速度慢导致去神经支配时间延长,修复通常会导致功能结果不佳。新的手术解决方案需要有效的临床前模型,以充分复制临床​​ PNI 的关键挑战。目的 开发猪 PNI 的临床前模型,解决 2 个具有挑战性的、临床相关的 PNI 场景:长节段性缺损(≥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。方法分别采用自体大隐神经或腓肠神经移植修复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。两种修复技术的相关解剖结构、手术方法和功能/组织学结果都进行了表征。结果 轴突在修复区再生并在远端残端被识别。电生理记录证实了这些发现,并建议再生轴突重新支配目标肌肉。结论 本文提出的模型提供了使用针对特定感兴趣机制(例如神经形态(运动、感觉、
更新日期:2020-05-11
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