PMID- 16636109 OWN - NLM STAT- MEDLINE DCOM- 20060719 LR - 20120215 IS - 1530-6860 (Electronic) IS - 0892-6638 (Linking) VI - 20 IP - 8 DP - 2006 Jun TI - Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages. PG - 1239-41 AB - 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. FAU - Bouhy, Delphine AU - Bouhy D AD - Research Center for Cellular and Molecular Neurobiology, University of Liege, Tour de Pathologie B36, 1etage, local 1/4A, CHU Sart-Tilman 4000 Liege, Belgium. FAU - Malgrange, Brigitte AU - Malgrange B FAU - Multon, Sylvie AU - Multon S FAU - Poirrier, Anne-Lise AU - Poirrier AL FAU - Scholtes, Felix AU - Scholtes F FAU - Schoenen, Jean AU - Schoenen J FAU - Franzen, Rachelle AU - Franzen R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060424 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - Axons/*drug effects/physiology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Female MH - Granulocyte-Macrophage Colony-Stimulating Factor/*therapeutic use MH - Kinetics MH - Macrophages/metabolism MH - Microglia/*metabolism MH - Motor Activity/drug effects MH - Nerve Fibers/drug effects/pathology/physiology MH - Nerve Regeneration/*drug effects MH - Neurites/drug effects MH - Paraplegia/*drug therapy/metabolism/physiopathology MH - Rats MH - Rats, Wistar EDAT- 2006/04/26 09:00 MHDA- 2006/07/20 09:00 CRDT- 2006/04/26 09:00 PHST- 2006/04/26 09:00 [pubmed] PHST- 2006/07/20 09:00 [medline] PHST- 2006/04/26 09:00 [entrez] AID - fj.05-4382fje [pii] AID - 10.1096/fj.05-4382fje [doi] PST - ppublish SO - FASEB J. 2006 Jun;20(8):1239-41. doi: 10.1096/fj.05-4382fje. Epub 2006 Apr 24.