Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages
[en] 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 mu g 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 GMCSF-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, D., Malgrange, B., Multon, S., Poirrier, A. L., Scholtes, F., Schoenen, J., Franzen, R. Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bouhy, Delphine
Malgrange, Brigitte ; Université de Liège - ULiège > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc.
Multon, Sylvie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
Poirrier, Anne-Lise ; Université de Liège - ULiège > Physiologie humaine et physiopathologie
Scholtes, Félix ; Université de Liège - ULiège > Département des sciences cliniques > Neurochirurgie
Schoenen, Jean ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
Franzen, Rachelle ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Neuro-anatomie
Language :
English
Title :
Delayed GM-CSF treatment stimulates axonal regeneration and functional recovery in paraplegic rats via an increased BDNF expression by endogenous macrophages
Publication date :
June 2006
Journal title :
FASEB Journal
ISSN :
0892-6638
eISSN :
1530-6860
Publisher :
Federation Amer Soc Exp Biol, Bethesda, United States - Maryland
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