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      Accumulation of connective tissue growth factor + cells during the early phase of rat traumatic brain injury

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          Abstract

          Abstract
          Background

          Glial scar formation is a common histopathological feature of traumatic brain injury (TBI). Astrogliosis and expression of transforming growth factor beta (TGF-β) are key components of scar formation and blood-brain barrier modulation. Connective tissue growth factor (CTGF) is considered a cytokine mediating the effects of TGF-β.

          Methods

          Here, we studied the CTGF expression in an open-skull weight-drop-induced TBI, with a focus on the early phase, most amenable to therapy.

          Results

          In normal rat brains of our study, CTGF + cells were rarely observed. Significant parenchymal accumulation of CTGF + non-neuron cells was observed 72 h post-TBI and increased continuously during the investigating time. We also observed that the accumulated CTGF + non-neuron cells were mainly distributed in the perilesional areas and showed activated astrocyte phenotypes with typical stellate morphologic characteristics.

          Conclusion

          Our observations demonstrated the time-dependent and lesion-associated accumulation of cellular CTGF expression in TBI, suggesting a pathological role of CTGF in TBI.

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          The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3963462091241165

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          Most cited references16

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          Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts.

          Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that binds heparin and is secreted by fibroblasts after activation with transforming growth factor beta (TGF-beta). CTGF is a member of a highly conserved family of peptides that include immediate early gene products cef10, cyr61, fisp12; a putative avian proto-oncogene, nov; and a drosophila gene, twisted gastrulation, tsg, that controls medial mesoderm induction during dorsal-ventral axis pattern formation, a process also controlled by TGF-beta related peptides (dpp, scw). In the adult mammal, CTGF functions as a downstream mediator of TGF-beta action on connective tissue cells, where it stimulates cell proliferation and extracellular matrix synthesis. CTGF does not appear to act on epithelial cells or immune cells. Because the biological actions of TGF-beta are complex and affect many different cell types, CTGF may serve as a more specific target for selective intervention in processes involving connective tissue formation during wound repair or fibrotic disorders. Northern blot and in situ hybridization studies have demonstrated that CTGF is coordinately expressed with TGF-beta in every fibrotic disorder examined to date. Agents that inhibit CTGF production or action could lead to the development of new therapeutic approaches for the control of fibrotic disorders in humans.
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            Astrocyte responses to CNS injury.

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              Effects of transforming growth factor beta 1 on scar production in the injured central nervous system of the rat.

              In the central nervous system (CNS), nerve regeneration after traumatic injury fails. The formation of a dense fibrous scar is thought to restrict in part the growth of axonal projections, providing one of the many reasons that complete lesions of neural pathways in the adult mammalian CNS are rarely followed by significant functional recovery. In order to determine which mechanisms mediate scar formation in the CNS and to investigate whether they can be modulated in vivo, we have attempted to define the potential role of trophic factors. Our previous studies have shown the focal elevation of transforming growth factor beta 1 (TGF beta 1) expression in lesioned CNS tissue. In the studies described here, we demonstrate that TGF beta 1 participates in the scarring response in the rat brain. First, the elevated protein levels of TGF beta 1 are localized to specific populations of injury-responsive cells in the traumatized CNS. Furthermore, the injection of TGF beta 1 into the brains of injured rats causes a dramatic increase in the scarring response. Conversely, when neutralizing TGF beta 1 antibodies are administered, the deposition of fibrous scar tissue and the formation of a limiting glial membrane that borders the lesion is significantly attenuated, thus establishing a role for the endogenous growth factor in regulation of the non-glial component of the scar. In implicating TGF beta 1 in the scarring response in the CNS, the potential use for TGF beta 1 antagonists as inhibitors of scar formation in the injured mammalian CNS is self-evident.
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                Author and article information

                Contributors
                Journal
                Diagn Pathol
                Diagn Pathol
                Diagnostic Pathology
                BioMed Central
                1746-1596
                2014
                10 July 2014
                : 9
                : 141
                Affiliations
                [1 ]Institute of Immunology, Third Military Medical University, 30 Gaotanyan Main Street, Chongqing 400038, People’s Republic of China
                [2 ]Institute of Brain Research, University of Tuebingen, Tuebingen, Germany
                Article
                1746-1596-9-141
                10.1186/1746-1596-9-141
                4227000
                25012526
                140d6875-2b16-41ec-b8dc-9756b6ab2530
                Copyright © 2014 Liu et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 15 March 2014
                : 1 July 2014
                Categories
                Research

                Pathology
                connective tissue growth factor,astrocytes,weight-drop model,traumatic brain injury
                Pathology
                connective tissue growth factor, astrocytes, weight-drop model, traumatic brain injury

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