Adult NG2+ cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury

J Neurosci. 2010 Jan 6;30(1):255-65. doi: 10.1523/JNEUROSCI.3705-09.2010.


We previously demonstrated that activated ED1+ macrophages induce extensive axonal dieback of dystrophic sensory axons in vivo and in vitro. Interestingly, after spinal cord injury, the regenerating front of axons is typically found in areas rich in ED1+ cells, but devoid of reactive astrocyte processes. These observations suggested that another cell type must be present in these areas to counteract deleterious effects of macrophages. Cells expressing the purportedly inhibitory chondroitin sulfate proteoglycan NG2 proliferate in the lesion and intermingle with macrophages, but their influence on regeneration is highly controversial. Our in vivo analysis of dorsal column crush lesions confirms the close association between NG2+ cells and injured axons. We hypothesized that NG2+ cells were growth promoting and thereby served to increase axonal stability following spinal cord injury. We observed that the interactions between dystrophic adult sensory neurons and primary NG2+ cells derived from the adult spinal cord can indeed stabilize the dystrophic growth cone during macrophage attack. NG2+ cells expressed high levels of laminin and fibronectin, which promote neurite outgrowth on the surface of these cells. Our data also demonstrate that NG2+ cells, but not astrocytes, use matrix metalloproteases to extend across a region of inhibitory proteoglycan, and provide a permissive bridge for adult sensory axons. These data support the hypothesis that NG2+ cells are not inhibitory to regenerating sensory axons and, in fact, they may provide a favorable substrate that can stabilize the regenerating front of dystrophic axons in the inhibitory environment of the glial scar.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Antigens / analysis
  • Antigens / biosynthesis*
  • Axons / chemistry
  • Axons / physiology
  • Cells, Cultured
  • Female
  • Macrophages / chemistry
  • Macrophages / cytology
  • Macrophages / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Regeneration / physiology*
  • Neurites / chemistry
  • Neurites / physiology*
  • Proteoglycans / analysis
  • Proteoglycans / biosynthesis*
  • Rats
  • Rats, Sprague-Dawley
  • Sensory Receptor Cells / chemistry
  • Sensory Receptor Cells / cytology
  • Sensory Receptor Cells / physiology*
  • Spinal Cord Injuries / physiopathology*


  • Antigens
  • Proteoglycans
  • chondroitin sulfate proteoglycan 4