Immediate Enhancement of Nerve Function Using a Novel Axonal Fusion Device After Neurotmesis

Abstract

BackgroundThe management of peripheral nerve injuries remains a large challenge for plastic surgeons. With the inability to fuse axonal endings, results after microsurgical nerve repair have been inconsistent. Our current nerve repair strategies rely upon the slow and lengthy process of axonal regeneration (~1 mm/d). Polyethylene glycol (PEG) has been investigated as a potential axonal fusion agent; however, the percentage of axonal fusion has been inconsistent. The purpose of this study was to identify a PEG delivery device to standardize outcomes after attempted axonal fusion with PEG.Materials and MethodsWe used a rat sciatic nerve injury model in which we completely transected and repaired the left sciatic nerve to evaluate the efficacy of PEG fusion over a span of 12 weeks. In addition, we evaluated the effectiveness of a delivery device's ability to optimize results after PEG fusion.ResultsWe found that PEG rapidly (within minutes) restores axonal continuity as assessed by electrophysiology, fluorescent retrograde tracer, and diffusion tensor imaging. Immunohistochemical analysis shows that motor axon counts are significantly increased at 1 week, 4 weeks, and 12 weeks postoperatively in PEG-treated animals. Furthermore, PEG restored behavioral functions up to 50% compared with animals that received the criterion standard epineurial repair (control animals).ConclusionsThe ability of PEG to rapidly restore nerve function after neurotmesis could have vast implications on the clinical management of traumatic injuries to peripheral nerves.

Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures, and behaviors lost after sciatic nerve transections in female rats

“…Qualitatively similar results are obtained for PEG-fused and negative control animals after completely ablating a 5-to 10-mm segment of a sciatic nerve and inserting an autograft or allograft to bridge the nerve gap Riley et al, 2015;Sexton et al, 2012). These data are also similar to data published by Thayer and his collaborators for single cut Bamba et al, 2017;Riley et al, 2017;Sexton et al, 2015) We have noted that features in electron micrographs of NMJs after PEG-fusion closely resemble those found in synaptic competition during development (Figure 9h; Smith et al, 2013).…”

“…These data are also similar to data published by Thayer and his collaborators for single cut (Bamba et al, 2016a, 2017; Sexton et al, 2015; ; Riley et al, 2017,) and to de Medinaceli (1983) who, perhaps inadvertently, used other fusogens in a study designed to test a device to microsuture very carefully trimmed nerve ends after a single transection.…”

“…In contrast, negative control animals rarely attained SFI scores of 270 by 42 days PO. Like those of PEGfused animals, negative control SFIs also reached a plateau at about 42 days and showed little improvement for months thereafter (Figure 1d and Bamba et al, 2017;Bittner et al, 2012;Bittner, Sengelaub, et al, 2016;Bittner, Sengelaub, Trevino, et al, 2017;Riley et al, 2017). These previous studies suggested that maintained survival of PEG-fused nerves was responsible for the remarkable recovery of SFI functional/behavioral scores obtained at 7-42 days PO, but never demonstrated axon survival in PEG-fused nerves, their absence in negative control nerves, or the possible contribution of naturally occurring outgrowth from severed, surviving axons proximal to the lesion site.…”

“…However, neither we nor any other author Bamba et al, 2017;Riley et al, 2017) has extensively examined the morphological and functional basis for these results-that is, the structure and/or function of severed distal axons, neuromuscular junctions (NMJs), and muscle fibers in PEG-fused versus unoperated or negative control sciatic nerves at 0-42 days PO. We have also never directly examined whether or how behavioral recovery at various PO days is due to (1) immediate reinnervation by axons that are artificially PEG-fused and then continuously maintained and/or (2) delayed reinnervation by natural regeneration of axons proximal to the lesion site.…”

Schwann Cell Supplementation in Neurosurgical Procedures after Neurotrauma

“…With an annual incidence of approximating 13 to 23 per 100,000 persons per year [1] the Peripheral Nerve Injuries (PNI), have a great impact in the people's quality of life. The expected recovery from this injuries depends on critical factors as the type of injury, the patient`s age and the delay before intervention [2]. However, it`s well known that after a PNI the Peripheral Nervous System (PNS) has an innate capacity to regenerate but is often insufficient and functional recovery is incomplete [3].…”