Polyethylene glycol-fused allografts produce rapid behavioral recovery after ablation of sciatic nerve segments

Abstract

Restoration of neuronal functions by outgrowths regenerating at ~1mm/d from the proximal stumps of severed peripheral nerves takes many weeks or months, if it occurs at all, especially after ablation of nerve segments. Distal segments of severed axons typically degenerate in 1–3 days. The purpose of this study was to show that Wallerian degeneration could be prevented or retarded and lost behavioral function restored following ablation of 0.5 – 1 cm segments of rat sciatic nerves in host animals. This is achieved using 0.8 – 1.1cm microsutured donor allografts treated with bioengineered solutions varying in ionic and polyethylene glycol (PEG) concentrations (modified PEG-fusion procedure), being careful not to stretch any portion of donor or host sciatic nerves. Our data show that PEG-fusion permanently restores axonal continuity within minutes as initially assessed by action potential conduction and intracellular diffusion of dye. Behavioral functions mediated by the sciatic nerve are largely restored within 2 – 4 wk as measured by the Sciatic Functional Index (SFI). Increased restoration of sciatic behavioral functions after ablating 0.5 – 1 cm segments is associated with greater numbers of viable myelinated axons within, and distal to, PEG-fused allografts. Many such viable myelinated axons are almost-certainly spared from Wallerian degeneration by PEG-fusion. PEG-fusion of donor allografts may produce a paradigm-shift in the treatment of peripheral nerve injuries.

Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures, and behaviors lost after sciatic nerve transections in female rats

“…We regard CAPs as only a “yes/no” (binary) measure of PEG-fusion success because CAP amplitude and time course depend on so many variables, including electrode shape, construction and placement, and numbers of axons having different diameters and myelin wrappings (Ghergherehchi et al, 2016). CAPs were evoked to assess electrophysiological function and continuity (Lore et al, 1999; Riley et al, 2015). Stimulating and recording electrodes were placed ~1cm apart across the site of intended transection and a CAP was recorded to confirm that the sciatic was intact and electrically viable.…”

Development of a Novel Suture-less Nerve Coaptation Device

“…Having this barbed inward projection will consequently produce outer surface fenestrations that can also facilitate placement of stem cells [11].or regeneration promoting factors like Polyethylene Glycol (PEG) [2]. Platelet Rich Plasma (PRP) or Fibroblast Growth Factor (FGF) [11].…”

“…Current strategies for peripheral nerve repair rely on regeneration or proximal outgrowth aided by microsutures, nerve grafts, or manufactured conduits [2,3]. However, even after repair, it can take months for regenerating axons to reach denervated target tissues when injuries are proximally located [1,4].…”

Bridging the Gap

“…17 For carbonic anhydrase II, primary antibody was used at 1:200 overnight. For choline acetyltransferase staining, primary antibody was used at 1:200 for 1 hour.…”