What is Normal? Neuromuscular junction reinnervation after nerve injury

Muscle Nerve. 2019 Nov;60(5):604-612. doi: 10.1002/mus.26654. Epub 2019 Aug 23.

Abstract

Introduction: In this study we present a reproducible technique to assess motor recovery after nerve injury via neuromuscular junction (NMJ) immunostaining and electrodiagnostic testing.

Methods: Wild-type mice underwent sciatic nerve transection with repair. Hindlimb muscles were collected for microscopy up to 30 weeks after injury. Immunostaining was used to assess axons (NF200), Schwann cells (S100), and motor endplates (α-bungarotoxin). Compound motor action potential (CMAP) amplitude was used to assess tibialis anterior (TA) function.

Results: One week after injury, nearly all (98.0%) endplates were denervated. At 8 weeks, endplates were either partially (28.3%) or fully (71.7%) reinnervated. At 16 weeks, NMJ reinnervation reached 87.3%. CMAP amplitude was 83% of naive mice at 16 weeks and correlated with percentage of fully reinnervated NMJs. Morphological differences were noted between injured and noninjured NMJs.

Discussion: We present a reproducible method for evaluating NMJ reinnervation. Electrodiagnostic data summarize NMJ recovery. Characterization of wild-type reinnervation provides important data for consideration in experimental design and interpretation.

Keywords: motor endplate; motor recovery; nerve injury; neuromuscular junction; reinnervation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Axons / pathology*
  • Bungarotoxins
  • Mice
  • Motor Endplate / pathology
  • Motor Endplate / physiopathology
  • Muscle Denervation
  • Muscle, Skeletal / innervation*
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Nerve Regeneration / physiology*
  • Neurofilament Proteins
  • Neuromuscular Junction / pathology*
  • Neuromuscular Junction / physiopathology
  • Neurosurgical Procedures
  • Recovery of Function
  • S100 Proteins
  • Schwann Cells / pathology*
  • Sciatic Nerve / injuries
  • Sciatic Nerve / surgery
  • Staining and Labeling
  • Wound Healing

Substances

  • Bungarotoxins
  • Neurofilament Proteins
  • S100 Proteins
  • neurofilament protein H