Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats

J Neurosci Res. 2018 Jul;96(7):1243-1264. doi: 10.1002/jnr.24227. Epub 2018 Apr 16.

Abstract

Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts. All results for Negative Control allografts agree with current neuroscience data 1-5 given above. Hence, PEG-fusion of allografts for repair of ablated peripheral nerve segments expand on previous observations in single-cut injuries, provoke reconsideration of some current neuroscience dogma, and further extend the potential of PEG-fusion in clinical practice.

Keywords: Wallerian degeneration; axotomy; nerve regeneration; nerve repair; polyethylene glycol; sciatic nerve.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allografts / drug effects
  • Animals
  • Axons / drug effects
  • Axons / physiology
  • Axotomy
  • Disease Models, Animal
  • Female
  • Muscle, Skeletal
  • Nerve Fibers / drug effects
  • Nerve Regeneration / drug effects*
  • Neural Conduction / drug effects
  • Neuromuscular Junction / drug effects
  • Peripheral Nerve Injuries / pathology
  • Peripheral Nerve Injuries / therapy
  • Peroneal Nerve / drug effects*
  • Peroneal Nerve / transplantation*
  • Polyethylene Glycols / pharmacology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Recovery of Function / drug effects
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiology
  • Sciatic Nerve / surgery
  • Sciatic Neuropathy / chemically induced
  • Sciatic Neuropathy / therapy*
  • Transplantation, Homologous
  • Wallerian Degeneration / prevention & control

Substances

  • Polyethylene Glycols