Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages.
Macrophages (monocytes/microglia) could play a critical role in central nervous system repair. We have previously found a synchronism between the regression of spontaneous axonal regeneration and the deactivation of macrophages 3-4 wk after a compression-injury of rat spinal cord. To explore whether reactivation of endogenous macrophages might be beneficial for spinal cord repair, we have studied the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in the same paraplegia model and in cell cultures. There was a significant, though transient, improvement of locomotor recovery after a single delayed intraperitoneal injection of 2 microg GM-CSF, which also increased significantly the expression of Cr3 and brain-derived neurotrophic factor (BDNF) by macrophages at the lesion site. At longer survival delays, axonal regeneration was significantly enhanced in GM-CSF-treated rats. In vitro, BV2 microglial cells expressed higher levels of BDNF in the presence of GM-CSF and neurons cocultured with microglial cells activated by GM-CSF generated more neurites, an effect blocked by a BDNF antibody. These experiments suggest that GM-CSF could be an interesting treatment option for spinal cord injury and that its beneficial effects might be mediated by BDNF.
Bouhy
Delphine
D
Research Center for Cellular and Molecular Neurobiology, University of Liège, Tour de Pathologie B36, 1étage, local 1/4A, CHU Sart-Tilman 4000 Liège, Belgium.
Malgrange
Brigitte
B
Multon
Sylvie
S
Poirrier
Anne-Lise
AL
Scholtes
Félix
F
Schoenen
Jean
J
Franzen
Rachelle
R
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009416:Nerve Regeneration / Q000187:drug effects*; D016501:Neurites / Q000187:drug effects; D010264:Paraplegia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
D019208:Brain-Derived Neurotrophic Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor