Spinal cord injury induction of lesional expression of profibrotic and angiogenic connective tissue growth factor confined to reactive astrocytes, invading fibroblasts and endothelial cells

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Abstract
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. 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%). 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.