A characterization of white matter pathology following spinal cord compression injury in the rat

R E Ward, W Huang, M Kostusiak, P N Pallier, A T Michael-Titus, J V Priestley

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Our laboratory has previously described the characteristics of neuronal injury in a rat compression model of spinal cord injury (SCI), focussing on the impact of this injury on the gray matter. However, white matter damage is known to play a critical role in functional outcome following injury. Therefore, in the present study, we used immunohistochemistry and electron microscopy to examine the alterations to the white matter that are initiated by compression SCI applied at T12 vertebral level. A significant loss of axonal and dendritic cytoskeletal proteins was observed at the injury epicenter within 1day of injury. This was accompanied by axonal dysfunction, as demonstrated by the accumulation of β-amyloid precursor protein (β-APP), with a peak at 3days post-SCI. A similar, acute loss of cytoskeletal proteins was observed up to 5mm away from the injury epicenter and was particularly evident rostral to the lesion site, whereas β-APP accumulation was prominent in tracts proximal to the injury. Early myelin loss was confirmed by myelin basic protein (MBP) immunostaining and by electron microscopy, which also highlighted the infiltration of inflammatory and red blood cells. However, 6weeks after injury, areas of new Schwann cell and oligodendrocyte myelination were observed. This study demonstrates that substantial white matter damage occurs following compression SCI in the rat. Moreover, the loss of cytoskeletal proteins and accumulation of β-APP up to 5mm away from the lesion site within 1day of injury indicates the rapid manner in which the axonal damage extends in the rostro-caudal axis. This is likely due to both Wallerian degeneration and spread of secondary cell death, with the latter affecting axons both proximal and distal to the injury.

Original languageEnglish
Pages (from-to)227-239
Number of pages13
JournalNeuroscience
Volume260
Early online date17 Dec 2013
DOIs
Publication statusPublished - 28 Feb 2014

Keywords

  • spinal cord injury
  • axons
  • demyelination
  • neurofilament
  • compression injury
  • white matter

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