title: Spinal cord injury induction of lesional expression of profibrotic and angiogenic connective tissue growth factor confined to reactive astrocytes, invading fibroblasts and endothelial cells.
abstract: OBJECTIVE
  The glial scar composed of astrogliosis and extracellular matrix deposition represents a major impediment to axonal regeneration. The authors investigated the role of a novel profibrotic and angiogenic peptide connective tissue growth factor (CTGF [Hcs24/IGFBP-r2P]) in glial scar formation following spinal cord injury (SCI) in rats.
  
  
  METHODS
  The effects of SCI on CTGF expression during glial scar maturation 1 day to 1 month post-SCI were investigated using fluorescein-activated cell sorter (FACS) immunohistochemical analysis; these findings were compared with those obtained in sham-operated (control) spinal cords. The CTGF-positive cells accumulated at the spinal cord lesion site (p < 0.0001) corresponding to areas of glial scar formation. In the perilesional rim, CTGF expression was confined to invading vimentin-positive, glial fibrillary acidic protein (GFAP)-negative fibroblastoid cells, endothelial and smooth-muscle cells of laminin-positive vessels, and GFAP-positive reactive astrocytes. The CTGF-positive astrocytes coexpressed the activation-associated intermediate filaments nestin, vimentin (> 80%), and mesenchymal scar component fibronectin (50%).
  
  
  CONCLUSIONS
  The restricted accumulation of CTGF-reactive astrocytes and CTGF-positive fibroblastoid cells lining the laminin-positive basal neolamina suggests participation of these cells in scar formation. In addition, perilesional upregulation of endothelial and smooth-muscle CTGF expression points to a role in blood-brain barrier function modulating edema-induced secondary damage.
authors.affiliation: Institute of Brain Research, University of Tübingen, Medical School, Tübingen, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Conrad
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Schluesener
authors.forename: Mehdi
authors.initials: M
authors.lastname: Adibzahdeh
authors.forename: Jan M
authors.initials: JM
authors.lastname: Schwab
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002921:Cicatrix / Q000473:pathology; D055513:Connective Tissue Growth Factor; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010784:Photomicrography; D051381:Rats; D011917:Rats, Inbred Lew; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: C526316:CCN2 protein, rat; D005353:Fibronectins; D005904:Glial Fibrillary Acidic Protein; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D014746:Vimentin; D055513:Connective Tissue Growth Factor