Abstract
The precise mechanisms of cortical damage in multiple sclerosis (MS) remain unknown. Microglia, the resident immune cells in the central nervous system (CNS), are involved in the chronic neuroinflammation in MS cortical lesions. Microglia produce various inflammatory cytokines such as IFN-γ and IL-β, reactive oxygen species, and glutamate. IL-β secretion is induced by NLRP3. ROS is induced by GM-CSF-producing Th17 cells. Glutamate is released via gap junctions. These molecules exert neurotoxicity. Meanwhile, damaged neurons produce fractalkine and FGF-2, which suppress microglial activation and enhance microglial neuroprotection through anti-inflammatory and anti-oxidant effect. Fractalkine accelerates microglial clearance of neuronal debris via inducing the release of MFG-E8. FGF-2 induces microglial migration through the FGFR3–Wnt–ERK signaling pathway. These molecules suppress microglial neuroinflammation, and enhance neuroprotection, which may give us clues for future therapeutic strategy cortical damage in MS.
