Previous studies have shown that RAGE and its ligand HMGB1 are highly expressed in active lesions of MS and its corresponding animal model of experimental autoimmune encephalomyelitis (EAE), in which microglia and macrophages are the main sources of HMGB1 in MS and EAE lesions, and that HMGB1 levels correlate with active inflammation. Here, HMGB1 is linked to experimental autoimmune encephalomyelitis.