Traumatically Induced Altered Membrane Permeability: Its Relationship to Traumatically Induced Reactive Axonal Change

J Neurotrauma. 1994 Oct;11(5):507-22. doi: 10.1089/neu.1994.11.507.

Abstract

Recent studies have suggested that severe forms of traumatic brain injury (TBI) can be associated with direct alterations of the axolemma. The present study evaluated whether injuries of mild to moderate severity are associated with comparable change. To this end, we used extracellular horseradish peroxidase (HRP) to determine if altered axolemmal permeability occurred following the traumatic event. Adult cats received intrathecal infusions of peroxidase and then were prepared for mild to moderate fluid percussion injury. At intervals ranging from 5 min to 3 h, animals were perfused with aldehydes and prepared for the histochemical visualization of the peroxidase, in addition to the immunocytochemical visualization of the neurofilament 68 kD subunit, a long recognized marker of reactive axonal change. The histochemically and immunocytochemically prepared tissue was examined at both the light and electron microscopic level. With mild TBI, the injured animals displayed a repertoire of neurofilament misalignment and axonal swelling consistent with that previously described in our laboratories, yet these changes were not associated with the passage of peroxidase from the extracellular to the intraaxonal compartment. With moderate injury, on the other hand, focal axolemmal permeability change to the extracellularly confined peroxidase was recognized. This peroxidase passage was associated with local mitochondrial abnormalities in addition to an increased packing of the neurofilaments. Over a 3 h course, these neurofilaments began to disassemble, showing a delayed progression of reactive axonal change. Collectively, the results of this investigation suggest that traumatically induced axonal injury involves complex subsets of pathobiology, one evoking rapid primary neurofilamentous change and misalignment, the other eliciting altered membrane permeability concomitant with rapid neurofilament compaction, leading to a delayed progression of reactive axonal change.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / metabolism
  • Axons / pathology
  • Axons / ultrastructure
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Cats
  • Cell Membrane Permeability
  • Histocytochemistry
  • Horseradish Peroxidase
  • Immunohistochemistry
  • Male
  • Microscopy, Electron
  • Mitochondria / ultrastructure
  • Neurofilament Proteins / metabolism
  • Percussion
  • Wounds, Nonpenetrating / metabolism
  • Wounds, Nonpenetrating / pathology

Substances

  • Neurofilament Proteins
  • neurofilament protein NF 68
  • Horseradish Peroxidase