Intrathecal granulocyte colony-stimulating factor modulate glial cell line-derived neurotrophic factor and vascular endothelial growth factor A expression in glial cells after experimental spinal cord ischemia.

Abstract

The hematopoietic growth factor, granulocyte colony-stimulating factor (G-CSF), has become one of the few growth factors approved for clinical use. It has therapeutic potential for numerous neurodegenerative diseases; however, at present the cellular effects of G-CSF on the central nervous system remain unclear and in need of investigation. In the present study, we used spinal cord ischemia, a neurodegenerative model, to examine the effects of intrathecal (i.t.) G-CSF on glial cell (microglia and astrocyte) activation and neuroprotective factor expression, including glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor A (VEGF-A) protein expression. Our results indicate that i.t. G-CSF could enhance ischemia-induced microglial activation and inhibit ischemia-induced astrocyte activation. Both GDNF and VEGF-A are upregulated after injury, and i.t. G-CSF could enhance GDNF and VEGF-A expressions after injury. Interestingly, our results indicate that performing i.t. G-CSF alone on normal animals could have the effect of microglial and astrocyte activation and enhanced GDNF and VEGF-A expressions. Furthermore, through laser scanning confocal microscopy, we found that astrocytes may contribute to the majority of GDNF and VEGF-A expressions of G-CSF after spinal cord ischemia. Overall, this G-CSF-induced upregulation suggests that activation of endogenous neuroprotective mechanisms could resist neurodegenerative insults. These observations demonstrate the cellular mechanism of i.t. G-CSF after spinal cord ischemia and confirm the neuroprotective effect of G-CSF after spinal cord ischemia injury.

• Authors: C-H Chen, S-Y Huang, N-F Chen, C-W Feng, H-C Hung, C-S Sung, Y-H Jean, Z-H Wen, W-F Chen
• Journal: Neuroscience (Neuroscience) Vol. 242 Pg. 39-52 (Jul 09 2013) ISSN: 1873-7544 [Electronic] United States
• PMID: 23548516 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Glial Cell Line-Derived Neurotrophic Factor
• Neuroprotective Agents
• Vascular Endothelial Growth Factor A
• Granulocyte Colony-Stimulating Factor

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Gene Expression Regulation (drug effects)
• Glial Cell Line-Derived Neurotrophic Factor (biosynthesis)
• Granulocyte Colony-Stimulating Factor (administration & dosage, pharmacology, therapeutic use)
• Injections, Spinal
• Ischemia (drug therapy, metabolism, pathology)
• Male
• Microglia (drug effects)
• Neuroprotective Agents (administration & dosage, pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Recovery of Function
• Spinal Cord (drug effects, pathology)
• Up-Regulation (drug effects)
• Vascular Endothelial Growth Factor A (biosynthesis)