Epineurial Window Is More Efficient in Attracting Axons than Simple Coaptation in a Sutureless (Cyanoacrylate-Bound) Model of End-to-Side Nerve Repair in the Rat Upper Limb: Functional and Morphometric Evidences and Review of the Literature

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.

Dynamic Quantitative Assessment of Motor Axon Sprouting after Direct Facial–Hypoglossal End-To-Side Neurorrhaphy in Rats

“…In fact, the number of regenerating myelinated nerve fibers in group ETS was approximately 70% of that in group ETE, and only 40% of the intact controls at the end of the study. This finding is largely in line with a study conducted by Papalia et al, 21 where less than 45% of the original axons were retained in the recipient nerve following ETS neurorrhaphy in the rat upper limb. Furthermore, there was an even larger gap on the number of labeled neurons giving regenerating axons between group ETE and group ETS.…”

“…Although regenerating axons are able to penetrate the epineurium and perineurium of the donor nerves, connective tissue sheath of the nerve does pose an obstacle to axon sprouting after ETS neurorrhaphy, 23 and research increasingly suggests that axonal damage in the donor nerve may provide a significant positive stimulus to axon sprouting. 11,21,[24][25][26] Therefore, it can reasonably be expected that ETS neurorrhaphy with deliberate injury in the donor hypoglossal nerve may result in larger numbers of regenerating fibers and better functional outcomes. It is worth mentioning that both the reconstruction techniques resulted in partial functional recovery at different levels, but no complete restoration of function was obtained.…”

Distal nerve transfer from the median nerve lumbrical fibers to the distal ulnar nerve motor branches in the palm: An anatomical cadaveric study

“…First, end‐to‐side coaptation could produce axon migration from the donor to the recipient nerve; moreover, it has been reported to be successful when applied to distal purely motor or sensate branches (Geuna et al, ; Papalia et al, ; Tos et al, ).…”

Effects of two intensities of treadmill exercise on neuromuscular recovery after median nerve crush injury in Wistar rats

“…Forelimb models have no contracture or autotomy that interferes in functional evaluation (Bertelli and Mira, 1995; Bontioti et al, 2003). Also, the grasping test is useful since the median nerve and finger flexor function can be easily assessed, furthermore, the grasping test is an objective and reliable method that allows researchers to track recovery progress during the repair process (Bertelli and Mira, 1995; Papalia et al, 2003, 2016; Ronchi et al, 2009).…”