Abstract

End-to-side nerve coaptation brings regenerating axons from the donor to the recipient nerve. Several techniques have been used to perform coaptation: microsurgical sutures with and without opening a window into the epi(peri)neurial connective tissue; among these, window techniques have been proven more effective in inducing axonal regeneration. The authors developed a sutureless model of end-to-side coaptation in the rat upper limb. In 19 adult Wistar rats, the median and the ulnar nerves of the left arm were approached from the axillary region, the median nerve transected and the proximal stump sutured to the pectoral muscle to prevent regeneration. Animals were then randomly divided in two experimental groups (7 animals each, 5 animals acting as control): Group 1: the distal stump of the transected median nerve was fixed to the ulnar nerve by applying cyanoacrylate solution; Group 2: a small epineurial window was opened into the epineurium of the ulnar nerve, caring to avoid damage to the nerve fibres; the distal stump of the transected median nerve was then fixed to the ulnar nerve by applying cyanoacrylate solution. The grasping test for functional evaluation was repeated every 10–11 weeks starting from week-15, up to the sacrifice (week 36). At week 36, the animals were sacrificed and the regenerated nerves harvested and processed for morphological investigations (high-resolution light microscopy as well as stereological and morphometrical analysis). This study shows that a) cyanoacrylate in end-to-side coaptation produces scarless axon regeneration without toxic effects; b) axonal regeneration and myelination occur even without opening an epineurial window, but c) the window is related to a larger number of regenerating fibres, especially myelinated and mature, and better functional outcomes.

Highlights

  • Animals were randomly divided in two experimental groups: 1. Group 1 (N-butyl-2-cyanoacrylate w/o epineurial window): the distal stump of the transected median nerve was fixed to the ulnar nerve by applying N-butyl-2-cyanoacrylate solution (7 animals); 2

  • Group 2 (N-butyl-2-cyanoacrylate with epineurial window): a small epineurial window was opened into the epineurium of the ulnar nerve, trying to avoid damage to the nerve fibres below; the distal stump of the transected median nerve was fixed to the ulnar nerve by applying N-butyl-2-cyanoacrylate solution (7 animals)

  • To investigate whether N-butyl-2-cyanoacrylate solution and the presence or not of the epineurial window can interfere with the regeneration, we first evaluated motor functional recovery after end-to-side coaptation, obtained at the time of the first evaluation and after 15, 25 and 36 weeks from the repair

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Summary

Introduction

A number of experimental [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17] as well as clinical [18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37] studies have shown that end-toside nerve coaptation is able to induce collateral sprouting from donor nerve’s axons, allowing for significant repopulation of the distal nerve stump.The injury to the donor nerve due to microsurgical suture in end-to-side coaptation, seems to be the starter of axonal growth and reinnervation in distal stump of receiving damaged nerve. Cyanoacrylates are a group of substances well-known and tested for their gluing properties and to date available for clinical use [43,44,45,46,47,48] Restrictions to their use in nerve coaptation have been registered by some authors [43,48], who detected that uncontrolled contamination by the gluing agent of the coapted nerve surfaces could produce local inflammation and a scar wall stopping nerve fibre regeneration. Their findings have been questioned by other studies, demonstrating that a transient inflammatory effect produced by cyanoacrylate in the coaptation zone is capable to stimulate local ingrowth of Schwann cells and connective tissue, creating the way for axonal sprouting [44,45,46,47]

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