Maresin 1 promotes inflammatory resolution, neuroprotection, and functional neurological recovery after spinal cord injury

Isaac Francos-Quijorna, Eva Santos-Nogueira, Karsten Gronert, Aaron B. Sullivan, Marcel A. Kopp, Benedikt Brommer, Samuel David, Jan M. Schwab, Ruben López-Vales

Producción científica: Contribución a una revistaArtículoInvestigaciónrevisión exhaustiva

126 Citas (Scopus)

Resumen

Resolution of inflammation is defective after spinal cord injury (SCI), which impairs tissue integrity and remodeling and leads to functional deficits. Effective pharmacological treatments for SCI are not currently available. Maresin 1 (MaR1) is a highly conserved specialized proresolving mediator (SPM) hosting potent anti-inflammatory and proresolving properties with potent tissue regenerative actions. Here, we provide evidence that the inappropriate biosynthesis of SPM in the lesioned spinal cord hampers the resolution of inflammation and leads to deleterious consequences on neurological outcome in adult female mice. We report that, after spinal cord contusion injury in adult female mice, the biosynthesis of SPM is not induced in the lesion site up to 2 weeks after injury. Exogenous administration of MaR1, a highly conserved SPM, propagated inflammatory resolution after SCI, as revealed by accelerated clearance of neutrophils and a reduction in macrophage accumulation at the lesion site. In the search of mechanisms underlying the proresolving actions of MaR1 in SCI, we found that this SPM facilitated several hallmarks of resolution of inflammation, including reduction of proinflammatory cytokines (CXCL1, CXCL2, CCL3, CCL4, IL6, and CSF3), silencing of major inflammatory intracellular signaling cascades (STAT1, STAT3, STAT5, p38, and ERK1/2), redirection of macrophage activation toward a prorepair phenotype, and increase of the phagocytic engulfment of neutrophils by macrophages. Interestingly, MaR1 administration improved locomotor recovery significantly and mitigated secondary injury progression in a clinical relevant model of SCI. These findings suggest that proresolution, immunoresol-vent therapies constitute a novel approach to improving neurological recovery after acute SCI.

Idioma originalInglés
Páginas (desde-hasta)11731-11743
Número de páginas13
PublicaciónJournal of Neuroscience
Volumen37
N.º48
DOI
EstadoPublicada - 29 nov 2017

Huella

Profundice en los temas de investigación de 'Maresin 1 promotes inflammatory resolution, neuroprotection, and functional neurological recovery after spinal cord injury'. En conjunto forman una huella única.

Citar esto