Elsevier

The Journal of Hand Surgery

Volume 43, Issue 1, January 2018, Pages 82.e1-82.e7
The Journal of Hand Surgery

Scientific article
Evaluation of a Nerve Fusion Technique With Polyethylene Glycol in a Delayed Setting After Nerve Injury

https://doi.org/10.1016/j.jhsa.2017.07.014Get rights and content

Purpose

Polyethylene glycol (PEG) has been hypothesized to restore axonal continuity using an in vivo rat sciatic nerve injury model when nerve repair occurs within minutes after nerve injury. We hypothesized that PEG could restore axonal continuity when nerve repair was delayed.

Methods

The left sciatic nerves of female Sprague-Dawley rats were transected and repaired in an end-to-end fashion using standard microsurgical techniques at 3 time points (1, 8, and 24 hours) after injury. Polyethylene glycol was delivered to the neurorrhaphy in the experimental group. Post-repair compound action potentials were immediately recorded after repair. Animals underwent behavioral assessments at 3 days and 1 week after surgery using the sciatic functional index test. The animals were sacrificed at 1 week to obtain axon counts.

Results

The PEG-treated nerves had improved compound action potential conduction and animals treated with PEG had improved sciatic function index. Compound action potential conduction was restored in PEG-fused rats when nerves were repaired at 1, 8, and 24 hours. In the control groups, no compound action potential conduction was restored when nerves were repaired. Sciatic functional index was superior in PEG-fused rats at 3 and 7 days after surgery compared with control groups at all 3 time points of nerve repair. Distal motor and sensory axon counts were higher in the PEG-treated rats.

Conclusions

Polyethylene glycol fusion is a new adjunct for nerve repair that allows rapid restoration of axonal continuity. It effective when delayed nerve repair is performed.

Clinical relevance

Nerve repair with application of PEG is a potential therapy that may have efficacy in a clinical setting. It is an experimental therapy that needs more investigation as well as clinical trials.

Section snippets

Experimental animals

Adult female Sprague-Dawley rats (250 g, Charles River Laboratories, Wilmington, MA) were used in this study. All experimental procedures were approved by the Institutional Animal Care and Use Committee at Vanderbilt University Medical Center.

Experimental design

Thirty female Sprague-Dawley rats were divided into 6 groups. A sciatic nerve injury model was used and all rats underwent complete nerve transection with a delayed nerve repair at 1 of 3 different time points (1, 8, or 24 hours). The times were chosen out

Electrophysiology data

Compound action potentials were evaluated at 2 time points: before injury and after repair. Electrophysiological studies showed that preinjury CAPs were present in all animals (n = 30) (Fig. 1). The CAP amplitudes were similar between experimental and control animals before complete transection of the sciatic nerve. After transection and delayed repair of the sciatic nerve at each group’s respective time point, no CAPs were recorded in any control animals. By contrast, CAP conduction was

Discussion

The current study provides electrophysiological, behavioral, and histological data for outcomes of PEG fusion in a rodent nerve injury model when performed up to 24 hours after injury. Further studies are needed to evaluate whether PEG can improve clinical outcomes and whether PEG improves outcomes even after 24 hours. The study contributes to a growing body of PEG fusion research that has traditionally focused on repair within minutes of injury.1, 2, 3, 4, 19

Our experience with PEG fusion in

Acknowledgments

This report was presented as a top paper at the 34th Annual Adrian E. Flatt Residents and Fellows Conference in Hand Surgery at the 2016 American Society for Surgery of the Hand annual meeting.

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    • Evolving Techniques in Peripheral Nerve Regeneration

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      Studies have shown a time-dependent decrease in the effectiveness of PEG fusion with delayed treatment.41 Although PEG fusion has been successfully performed up to 24 hours after an injury, it seems unlikely that the window for this intervention can be extended beyond 1 day because of the inevitable initiation of Wallerian degeneration.42 The window of the effectiveness of PEG fusion could be widened if future work identifies techniques to delay the onset of Wallerian degeneration long enough to affect operative repair using PEG fusion.

    • Fusogens: chemical agents that can rapidly restore function after nerve injury

      2019, Journal of Surgical Research
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      The patients were part of a clinical trial run through Vanderbilt University (NCT02359825) and patient enrollment continues. More recently, the same group evaluated PEG-mediated nerve repair in the sciatic nerves of rats in a delayed fashion (up to 24 h after injury) and found that functional recovery was still possible.20 The implications of these early clinical findings are profound.

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    This work was supported by the Department of Defense and National Institutes of Health (NIH) grant numbers OR120216 and NIH EB001744. The toluidine blue staining and analysis were performed in part through the use of the Vanderbilt University Medical Center Cell Imaging Shared Resource (supported by NIH grants CA68485, DK20593, DK58404, DK59637, and EY08126).

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