Polyethylene Glycol (PEG) and Other Bioactive Solutions with Neurorrhaphy for Rapid and Dramatic Repair of Peripheral Nerve Lesions by PEG-fusion

Overview

Journal J Neurosci Methods

Specialty Neurology

Date 2018 Dec 27

PMID 30586569

Citations 21

Authors

Cameron L Ghergherehchi

Michelle Mikesh

Dale R Sengelaub

David M Jackson

Tyler Smith

Jacklyn Nguyen

Jaimie T Shores

George D Bittner

Affiliations

Soon will be listed here.

Abstract

Background: Nervous system injuries in mammals often involve transection or segmental loss of peripheral nerves. Such injuries result in functional (behavioral) deficits poorly restored by naturally occurring 1-2 mm/d axonal outgrowths aided by primary repair or reconstruction. "Neurorrhaphy" or nerve repair joins severed connective tissues, but not severed cytoplasmic/plasmalemmal extensions (axons) within the tissue.

New Method: PEG-fusion consists of neurorrhaphy combined with a well-defined sequence of four pharmaceutical agents in solution, one containing polyethylene glycol (PEG), applied directly to closely apposed viable ends of severed axons.

Results: PEG-fusion of rat sciatic nerves: (1) restores axonal continuity across coaptation site(s) within minutes, (2) prevents Wallerian degeneration of many distal severed axons, (3) preserves neuromuscular junctions, (4) prevents target muscle atrophy, (5) produces rapid and improved recovery of voluntary behaviors compared with neurorrhaphy alone, and (6) PEG-fused allografts are not rejected, despite no tissue-matching nor immunosuppression.

Comparison With Existing Methods: If PEG-fusion protocols are not correctly executed, the results are similar to that of neurorrhaphy alone: (1) axonal continuity across coaptation site(s) is not re-established, (2) Wallerian degeneration of all distal severed axons rapidly occurs, (3) neuromuscular junctions are non-functional, (4) target muscle atrophy begins within weeks, (5) recovery of voluntary behavior occurs, if ever, after months to levels well-below that observed in unoperated animals, and (6) allografts are either rejected or not well-accepted.

Conclusion: PEG-fusion produces rapid and dramatic recovery of function following rat peripheral nerve injuries.

Citing Articles

An analysis of differential gene expression in peripheral nerve and muscle utilizing RNA sequencing after polyethylene glycol nerve fusion in a rat sciatic nerve injury model.

Weiss S, Legato J, Liu Y, Vaccaro C, Pellegrino da Silva R, Miskiel S PLoS One. 2024; 19(9):e0304773.

PMID: 39231134 PMC: 11373823. DOI: 10.1371/journal.pone.0304773.

Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion.

Smith T, Zhou L, Ghergherehchi C, Mikesh M, Yang C, Tucker H Neural Regen Res. 2024; 20(4):1192-1206.

PMID: 38989956 PMC: 11438327. DOI: 10.4103/NRR.NRR-D-23-01220.

Interpretation of Data from Translational Rodent Nerve Injury and Repair Models.

Marsh E, Snyder-Warwick A, Mackinnon S, Wood M Hand Clin. 2024; 40(3):429-440.

PMID: 38972687 PMC: 11228394. DOI: 10.1016/j.hcl.2024.03.004.

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains.

Zhou L, Venkudusamy K, Hibbard E, Montoya Y, Olivarez A, Yang C Neural Regen Res. 2024; 20(9):2667-2681.

PMID: 38934383 PMC: 11801302. DOI: 10.4103/NRR.NRR-D-23-01846.

Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord.

Hibbard E, Zhou L, Yang C, Venkudusamy K, Montoya Y, Olivarez A Neural Regen Res. 2024; 20(7):2095-2107.

PMID: 38845228 PMC: 11691455. DOI: 10.4103/NRR.NRR-D-23-01845.

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