Differential Cellular Accumulation of Connective Tissue.pdf

JOURNAL OF NEUROTRAUMA Volume 18, Number 4, 2001 Mary Ann Liebert, Inc. Differential Cellular Accumulation of Connective Tissue Growth Factor Defines a Subset of Reactive Astrocytes, Invading Fibroblasts, and Endothelial Cells Following Central Nervous System Injury in Rats and Humans JAN MARKUS SCHWAB, RUDI BESCHORNER, THAI DUNG NGUYEN, RICHARD MEYERMANN, and HERMANN J. SCHLUESENER ABSTRACT In brain injury, the primary trauma is followed by a cascade of cellular and molecular mechanisms resulting in secondary injury and scar formation. Astrogliosis and expression of transforming growth factor beta (TGF-b ) are key components of scar formation. A cytokine mediating the effects of TGF- b is connective tissue growth factor (CTGF), a fibrogenic peptide encoded by an immediate early gene with suggested roles in tissue regeneration and aberrant deposition of extracellular matrix. In order to investigate CTGF in traumatic lesions, we evaluated 20 human brains with traumatic brain injury (TBI) and 18 rat brains with stab wound injury. Compared to remote areas and unaltered control brains, CTGF 1 cells accumulated in border zones of the traumatic lesion site (p , 0.0001). In the direct peri-lesional rim, CTGF expression was confined to invading vimentin 1 , GFAP2 fi- broblastoid cells, endothelial and smooth muscle cells of laminin 1 vessels, and GFAP1 reactive as- trocytes. In the direct peri-lesional rim, CTGF 1 astrocytes (.80%) co-expressed the activation as- sociated intermediate filaments nestin and vimentin. In injured rat brains, numbers of CTGF 1 cells peaked at day 3 and 7 and decreased to almost base level 3 weeks postinjury, whereas in humans, CTGF 1 cells remained persistently elevated up to 6 months (p , 0.0001). The restricted accumula- tion of CTGF 1 -reactive astrocytes and CTGF 1 fibroblastoid cells lining the adjacent laminin 1 ba- sal lamina suggests participation of these cells in scar formation. Furthermore, peri-lesional upreg- ulation of endothelia