Indexado en

Licencia y uso

Citaciones

Cited 121 times in

Cited 111 times in

Altmetrics

Grant support

This work was supported by the Spanish Ministry of Economy and Competitiveness (Grants SAF2010-17851 and SAF2013-48431-R to R.L-V.), the International Foundation for Research in Paraplegia (R.L-V.), and the Fondo de Investigacion Sanitaria of Spain (TERCEL and CIBERNED; R.L-V.). J.M.S. received funding from the Wings for Life Spinal Cord Research Foundation, the Era-Net-NEURON Program of the European Union (SILENCE Grant #01EW170A), NIDILRR (Grant #90SI5020), and the W.E. Hunt & C.M. Curtis Endowment. K.G. received funding from the National Institutes of Health (Grant EY026082).

Análisis de autorías institucional

Compartir

Maresin 1 Promotes Inflammatory Resolution, Neuroprotection, and Functional Neurological Recovery After Spinal Cord Injury

Publicado en:JOURNAL OF NEUROSCIENCE. 37 (48): 11731-11743 - 2017-11-29 37(48), DOI: 10.1523/JNEUROSCI.1395-17.2017

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

Afiliaciones

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, immunoresolvent therapies constitute a novel approach to improving neurological recovery after acute SCI.

Palabras clave