title: Acute granulocyte macrophage-colony stimulating factor treatment modulates neuroinflammatory processes and promotes tactile recovery after spinal cord injury.
abstract: Neuroinflammation is known to play a key role in the prognosis of functional recovery after spinal cord injury (SCI). The involvement of microglial and mast cells in early and late stages of inflammation has been receiving increasing attention. This study was aimed at determining the influence of a pro-inflammatory cytokine, the granulocyte macrophage-colony stimulating factor (GM-CSF), on microglia and mast cell activation, glial scar formation and functional recovery following SCI. Rats were randomly injected with saline or GM-CSF one hour after a C4-C5 medio-lateral hemisection. To assess functional impairment and recovery, the rats were subjected to sensorimotor tasks for one month. Then, responses evoked by forepaw stimulation in the primary somatosensory cortex were recorded. We also quantified the changes in GM-CSF, IL-1β, IL-6 and BDNF levels, the gliosis and lesion volume as well as microglial and mast cell density, and mast cell surface. Our findings show that GM-CSF promotes cortical reactivation and recovery of tactile abilities, whereas it does not influence motor performances. A transient decrease in pro-inflammatory cytokines after GM-CSF treatment was also observed, whereas the endogenous GM-CSF level was unchanged. While the beneficial role of GM-CSF in reducing glial scar is confirmed, our findings reveal that neuroinflammatory events mediated by microglial and mast cells as well as the alteration of IL-1β and IL-6 levels are paralleled with an improvement in tactile recovery. These mechanisms could limit the duration and intensity of homeostatic imbalance and promote the plasticity of spared tissues.
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Intégratives et Adaptatives, Marseille, France.
authors.forename: Sandie
authors.initials: S
authors.lastname: Thomaty
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Intégratives et Adaptatives, Marseille, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Pezard
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Intégratives et Adaptatives, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Xerri
authors.affiliation: Aix-Marseille Université, CNRS, UMR 7260, Laboratoire de Neurosciences Intégratives et Adaptatives, Marseille, France. Electronic address: jean-michel.brezun@univ-amu.fr.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Brezun
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005911:Gliosis; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000187:drug effects / Q000473:pathology; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: forepaw representation; functional recovery; granulocyte macrophage-colony stimulating factor; neuro-inflammation; somatosensory cortex; spinal cord injury