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
Article first published online: 29 MAR 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 58, Issue 9, pages 1074–1081, July 2010
How to Cite
Shen, L. H., Li, Y. and Chopp, M. (2010), 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. Glia, 58: 1074–1081. doi: 10.1002/glia.20988
- Issue published online: 7 MAY 2010
- Article first published online: 29 MAR 2010
- Manuscript Accepted: 22 FEB 2010
- Manuscript Received: 23 DEC 2009
- bone marrow stromal cells;
- reactive astrocytes
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 × 106 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.