Polyethylene glycol (PEG) and other bioactive solutions with neurorrhaphy for rapid and dramatic repair of peripheral nerve lesions by PEG-fusion.

Allografts Animals Axons / drug effects Disease Models, Animal Female Male Neuromuscular Junction / pathology Neuroprotective Agents / pharmacology Neurosurgical Procedures / methods Polyethylene Glycols / pharmacology Random Allocation Rats, Sprague-Dawley Sciatic Nerve / drug effects Suture Techniques Wallerian Degeneration / prevention & control
Allograft Neuromuscular junction re-innervation Neurorrhaphy Peripheral nerve injury Polyethylene glycol fusion Rat sciatic nerve repair Wallerian degeneration

Journal

Journal of neuroscience methods
ISSN: 1872-678X
Titre abrégé: J Neurosci Methods
Pays: Netherlands
ID NLM: 7905558

Informations de publication

Date de publication:
15 02 2019
Historique:
received: 31 07 2018
revised: 17 12 2018
accepted: 19 12 2018
pubmed: 27 12 2018
medline: 18 6 2020
entrez: 27 12 2018
Statut: ppublish

Résumé

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

Sections du résumé

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.

Identifiants

DOI: 10.1016/j.jneumeth.2018.12.015 PMID: 30586569 PMC: PMC6475191
pubmed: 30586569
pii: S0165-0270(18)30413-8
doi: 10.1016/j.jneumeth.2018.12.015
pmc: PMC6475191
mid: NIHMS1518360
pii:
doi:

Substances chimiques

Neuroprotective Agents 0
Polyethylene Glycols 3WJQ0SDW1A

Types de publication

Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

1-12

Subventions

Organisme : NINDS NIH HHS
ID : R01 NS081063
Pays : United States

Informations de copyright

Copyright © 2019 Elsevier B.V. All rights reserved.

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Auteurs

Cameron L Ghergherehchi (CL)

Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA. Electronic address: cameronlgh@utexas.edu.

Michelle Mikesh (M)

Department of Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA. Electronic address: mfmikesh@utexas.edu.

Dale R Sengelaub (DR)

Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, USA. Electronic address: sengelau@indiana.edu.

David M Jackson (DM)

Neuraptive Therapeutics, Lafayette, CO, USA. Electronic address: david.jackson@neuraptive.com.

Tyler Smith (T)

Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, 78712, USA. Electronic address: tylersmith128@utexas.edu.

Jacklyn Nguyen (J)

Department of Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA. Electronic address: jacklyn.nguyen@utexas.edu.

Jaimie T Shores (JT)

Department of Plastic and Reconstructive Surgery, Vascularized Composite Allotransplantation (VCA) Laboratory, Johns Hopkins University School of Medicine, Ross Research Building 749D, 720 Rutland Avenue, Baltimore, MD, 21205, USA. Electronic address: jshores3@jhmi.edu.

George D Bittner (GD)

Department of Neuroscience, University of Texas at Austin, Austin, TX, 78712, USA. Electronic address: bittner@austin.utexas.edu.

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Classifications MeSH

questionsmedicales.fr › Régions du corps › Transplants › Allogreffes › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Eucaryotes › Animaux › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Cellules › Neurones › Neurofibres › Axones › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Cellules › Structures cellulaires › Membrane cellulaire › Structures de la membrane cellulaire › Jonctions intercellulaires › Synapses › Synapse neuro-effectrice › Jonction neuromusculaire › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Agents du système nerveux central › Neuroprotecteurs › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Procédures de chirurgie opératoire › Procédures de neurochirurgie › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Technologie, industrie et agriculture › Produits manufacturés › Matériaux biomédicaux et dentaires › Polymères › Polyéthylène glycols › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Répartition aléatoire › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Rat Sprague-Dawley › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Système nerveux › Système nerveux périphérique › Nerfs périphériques › Nerfs spinaux › Plexus lombosacral › Nerf ischiatique › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › Procédures de chirurgie opératoire › Techniques de fermeture des plaies › Techniques de suture › Polyethylene glycol (PEG) and other bioactive...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Dégénérescence nerveuse › Dégénérescence wallerienne › Polyethylene glycol (PEG) and other bioactive...