This article shows that specialized proresolving mediator (SPM) biosynthesis is impaired after spinal cord injury (SCI) and that systemic administration of Maresin 1 (MaR1), a highly conserved SPM, is able to enhance resolution of inflammation, resulting in improved functional and histopathological outcomes. The authors provide evidence 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 propagated inflammatory resolution after SCI, as revealed by accelerated clearance of neutrophils and a reduction in macrophage accumulation at the lesion site. The study 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. These results provide strong evidence about the beneficial effects of exogenous administration of MaR1 in a preclinical model of SCI and suggest that administration of SPMs could be a novel therapeutic approach to treat acute SCI in humans, for which there is currently no effective treatment.
