Changes in distribution, cell associations, and protein expression levels of NG2, neurocan, phosphacan, brevican, versican v2, and tenascin-C during acute to chronic maturation of spinal cord scar tissue

Xiufeng Tang, Jeannette E. Davies, Stephen J.A. Davies

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298 Citations (Scopus)

Abstract

Previous studies have correlated the failure of axon regeneration after spinal cord injury with axons contacting scar tissue rich in chondroitin sulfate proteoglycans (CSPGs; Davies et al., 1999). In the present study, we have conducted immunohistochemical and quantitative Western blot analysis of five axon-growth-inhibitory CSPGs and tenascin-C within stab injuries of adult rat spinal cord at time points ranging from 24 hr to 6 months post injury. Quantitative Western blot analysis showed robust increases in neurocan, tenascin-C, and NG2 levels by 24 hr, suggesting that these molecules play a role in preventing axon regeneration across acutely forming scar tissue. Peak levels of 245/130 kD neurocan, NG2, and 250/200 kD tenascin-C were reached at 8 days, with maximum levels of phosphacan and 140/80 kD brevican attained later, at 1 month post injury. Versican V2 protein levels, however, displayed an opposite trend, dropping below unlesioned spinal cord values at all time points studied. Confocal microscopy at 8 days post injury revealed heightened immunoreactivity for phosphacan, NG2, and tenascin-C, particularly within fibronectin+ scar tissue at lesion centers. In contrast, neurocan was displayed within lesion margins on the processes of stellate NG2+ cells and, to a much lesser extent, by astrocytes. At 6 months post injury, 130 kD neurocan, brevican, and NG2 levels within chronic scar tissue remained significantly above control. Our results show novel expression patterns and cell associations of inhibitory CSPGs and tenascin-C that have important implications for axon regeneration across acute and chronic spinal cord scar tissue.

Original languageEnglish
Pages (from-to)427-444
Number of pages18
JournalJournal of Neuroscience Research
Volume71
Issue number3
DOIs
Publication statusPublished - 1 Feb 2003
Externally publishedYes

Keywords

  • Extracellular matrix
  • Glial scar
  • Inhibitory proteoglycans
  • Regeneration

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