Spinal cord injury induction of lesional expression of profibrotic and angiogenic connective tissue growth factor confined to reactive astrocytes, invading fibroblasts and endothelial cells.
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.
Conrad
Sabine
S
Institute of Brain Research, University of Tübingen, Medical School, Tübingen, Germany.
Schluesener
Hermann J
HJ
Adibzahdeh
Mehdi
M
Schwab
Jan M
JM
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
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