Melatonin promotes microglia toward anti-inflammatory phenotype after spinal cord injury

Microglia, immune cells in the central nervous system (CNS), mediate inflammatory responses and provide support to the microenvironment. Neurotoxic microglia predominantly locate in the injured spinal cord that delay spinal cord injury (SCI) repair. We previously found that melatonin could suppress SCI-induced neuronal inflammatory activation. However, the effect of melatonin in microglia responses remains unclear. In this study, isolated primary microglia and neurons were stimulated with lipopolysaccharide (LPS) and interferon-γ (IFN-γ) or melatonin-containing medium. We found that melatonin supported the beneficial polarization from pro-inflammatory to anti-inflammation, downrehulated ROS activity, and recovered mitochondrial metabolism in vitro and in vivo. Furthermore, melatonin downregulated pro-inflammatory-related mRNA levels. These results suggested that melatonin may be therapeutic potential for neuroinflammation-related neurological disorders, such as SCI.