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Astrocytic endogenous glial cell derived neurotrophic factor production is enhanced by bone marrow stromal cell transplantation in the ischemic boundary zone after stroke in adult rats
Author(s) -
Shen L. H.,
Li Y.,
Chopp M.
Publication year - 2010
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20988
Subject(s) - glial cell line derived neurotrophic factor , neurotrophic factors , biology , glial fibrillary acidic protein , subventricular zone , stromal cell , neuroblast , transplantation , astrocyte , endocrinology , microbiology and biotechnology , medicine , immunology , cancer research , stem cell , immunohistochemistry , progenitor cell , neurogenesis , central nervous system , biochemistry , receptor
Bone marrow stromal cells (BMSCs) facilitate functional recovery in rats after focal ischemic attack. Growing evidence suggests that the secretion of various bioactive factors underlies BMSCs' beneficial effects. This study investigates the expression of glial cell derived neurotrophic factor (GDNF) in the ischemic hemisphere with or without BMSC administration. Adult male Wistar rats were subjected to 2 h of middle cerebral artery occlusion followed by an injection of 3 × 10 6 BMSCs ( n = 11) or phosphate‐buffered saline ( n = 10) into the tail vein 24 h later. Animals were sacrificed seven days later. Single and double immunohistochemical staining was performed to measure GDNF, Ki67, doublecortin, and glial fibrillary acidic protein expression as well as the number of apoptotic cells along the ischemic boundary zone (IBZ) and/or in the subventricular zone (SVZ). BMSC treatment significantly increased GDNF expression and decreased the number of apoptotic cells in the IBZ ( P < 0.05). GDNF expression was colocalized with GFAP. Meanwhile, BMSCs increased the number of Ki‐67 positive cells and the density of DCX positive migrating neuroblasts ( P < 0.05). GDNF expression was significantly increased in single astrocytes collected from animals treated with BMSCs, and in astrocytes cocultured with BMSCs after OGD ( P < 0.05). Our data suggest that BMSCs increase GDNF levels in the ischemic hemisphere; the major source of GDNF protein is reactive astrocytes. We propose that the increase of GDNF in response to BMSC administration creates a hospitable environment for local cellular repair as well as for migrating neuroblasts from the SVZ, and thus contributes to the functional improvement. © 2010 Wiley‐Liss, Inc.