Chronic peripheral nerve compression disrupts paranodal axoglial junctions

Muscle Nerve. 2017 Apr;55(4):544-554. doi: 10.1002/mus.25273. Epub 2016 Dec 26.

Abstract

Introduction: Peripheral nerves are often exposed to mechanical stress leading to compression neuropathies. The pathophysiology underlying nerve dysfunction by chronic compression is largely unknown.

Methods: We analyzed molecular organization and fine structures at and near nodes of Ranvier in a compression neuropathy model in which a silastic tube was placed around the mouse sciatic nerve.

Results: Immunofluorescence study showed that clusters of cell adhesion complex forming paranodal axoglial junctions were dispersed and overlapped frequently with juxtaparanodal components. These paranodal changes occurred without internodal myelin damage. The distribution and pattern of paranodal disruption suggests that these changes are the direct result of mechanical stress. Electron microscopy confirmed loss of paranodal axoglial junctions.

Conclusions: Our data show that chronic nerve compression disrupts paranodal junctions and axonal domains required for proper peripheral nerve function. These results provide important clues toward better understanding of the pathophysiology underlying nerve dysfunction in compression neuropathies. Muscle Nerve 55: 544-554, 2017.

Keywords: axon-glia interactions; compression neuropathy; mouse model; node of Ranvier; paranodal junction.

Publication types

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

MeSH terms

  • Animals
  • Ankyrins / metabolism
  • Arthrogryposis / pathology*
  • Arthrogryposis / physiopathology*
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Disease Models, Animal
  • Evoked Potentials, Motor / physiology*
  • Female
  • Functional Laterality
  • Gene Expression Regulation
  • Hereditary Sensory and Motor Neuropathy / pathology*
  • Hereditary Sensory and Motor Neuropathy / physiopathology*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Electron, Transmission
  • Nerve Growth Factors / metabolism
  • Neural Conduction / physiology
  • Ranvier's Nodes / metabolism*
  • Ranvier's Nodes / pathology
  • Ranvier's Nodes / ultrastructure
  • Sciatic Nerve / pathology
  • Sciatic Nerve / physiopathology
  • Sciatic Nerve / ultrastructure
  • Shab Potassium Channels / metabolism

Substances

  • Ank3 protein, mouse
  • Ankyrins
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Cntnap1 protein, mouse
  • Nerve Growth Factors
  • Nfasc protein, mouse
  • Shab Potassium Channels
  • gliomedin protein, mouse

Supplementary concepts

  • Tomaculous neuropathy