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在聚乙二醇存在下进行神经缝合可使猪面神经损伤模型实现即时电生理传导。

Neurorrhaphy in Presence of Polyethylene Glycol Enables Immediate Electrophysiological Conduction in Porcine Model of Facial Nerve Injury.

作者信息

Petrov Dmitriy, Burrell Justin C, Browne Kevin D, Laimo Franco A, Roberts Sanford E, Ali Zarina S, Cullen D Kacy

机构信息

Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States.

Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, PA, United States.

出版信息

Front Surg. 2022 Mar 7;9:811544. doi: 10.3389/fsurg.2022.811544. eCollection 2022.

Abstract

Facial nerve trauma often leads to disfiguring facial muscle paralysis. Despite several promising advancements, facial nerve repair procedures often do not lead to complete functional recovery. Development of novel repair strategies requires testing in relevant preclinical models that replicate key clinical features. Several studies have reported that fusogens, such as polyethylene glycol (PEG), can improve functional recovery by enabling immediate reconnection of injured axons; however, these findings have yet to be demonstrated in a large animal model. We first describe a porcine model of facial nerve injury and repair, including the relevant anatomy, surgical approach, and naive nerve morphometry. Next, we report positive findings from a proof-of-concept experiment testing whether a neurorrhaphy performed in conjunction with a PEG solution maintained electrophysiological nerve conduction at an acute time point in a large animal model. The buccal branch of the facial nerve was transected and then immediately repaired by direct anastomosis and PEG application. Immediate electrical conduction was recorded in the PEG-fused nerves ( = 9/9), whereas no signal was obtained in a control cohort lacking calcium chelating agent in one step ( = 0/3) and in the no PEG control group ( = 0/5). Nerve histology revealed putative-fused axons across the repair site, whereas no positive signal was observed in the controls. Rapid electrophysiological recovery following nerve fusion in a highly translatable porcine model of nerve injury supports previous studies suggesting neurorrhaphy supplemented with PEG may be a promising strategy for severe nerve injury. While acute PEG-mediated axon conduction is promising, additional work is necessary to determine if physical axon fusion occurs and the longer-term fate of distal axon segments as related to functional recovery.

摘要

面神经创伤常导致毁容性的面部肌肉麻痹。尽管有一些很有前景的进展,但面神经修复手术往往不能带来完全的功能恢复。开发新的修复策略需要在能够复制关键临床特征的相关临床前模型中进行测试。几项研究报告称,诸如聚乙二醇(PEG)之类的融合剂可通过使受损轴突立即重新连接来改善功能恢复;然而,这些发现尚未在大型动物模型中得到证实。我们首先描述一种面神经损伤与修复的猪模型,包括相关解剖结构、手术方法和原始神经形态测量。接下来,我们报告一项概念验证实验的阳性结果,该实验测试在大型动物模型中,与PEG溶液联合进行的神经缝合术在急性时间点是否能维持神经电生理传导。面神经颊支被切断,然后通过直接吻合和应用PEG立即进行修复。在PEG融合的神经中记录到了即时电传导(n = 9/9),而在一步中缺乏钙螯合剂的对照组(n = 0/3)和无PEG对照组(n = 0/5)中未获得信号。神经组织学显示在修复部位有假定融合的轴突,而在对照组中未观察到阳性信号。在一个具有高度可转化性的神经损伤猪模型中,神经融合后快速的电生理恢复支持了先前的研究,表明补充PEG的神经缝合术可能是治疗严重神经损伤的一种有前景的策略。虽然急性PEG介导的轴突传导很有前景,但还需要进一步的工作来确定是否发生了物理性轴突融合以及与功能恢复相关的远端轴突段的长期命运。

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