Acute granulocyte macrophage-colony stimulating factor treatment modulates neuroinflammatory processes and promotes tactile recovery after spinal cord injury. (4th May 2017)

• Record Type: Journal Article
• Authors: Thomaty, Sandie; Pezard, Laurent; Xerri, Christian; Brezun, Jean-Michel
• Is Part Of: Neuroscience. Volume 349(2017)
• Page Start: 144
• Page End: 164
• Publication Date: 2017-05-04
• Subjects: CNS central nervous system -- CSF cerebrospinal fluid -- GFAP Glial Fibrillary Acidic Protein -- GM-CSF granulocyte macrophage-colony stimulating factor -- PBS phosphate-buffered saline -- SCI spinal cord injury; spinal cord injury -- granulocyte macrophage-colony stimulating factor -- neuro-inflammation -- functional recovery -- forepaw representation -- somatosensory cortex; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2017.02.035
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: GM-CSF modulates inflammation through microglial and mast cell activation after SCI. GM-CSF treatment reduces the glial scar without change in the lesion size. GM-CSF promotes reactivation in S1 aera and recovery of tactile abilities after SCI. 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.