High salt diet intake promotes the induction of experimental autoimmune encephalomyelitis by exacerbating neutrophil infiltration and microglial activation.

Although the cause of multiple sclerosis (MS) is not fully known, environmental and lifestyle factors are considered significant risk factors for its development and progression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we found that dietary high salt (HS) intake significantly exacerbated the clinical scores of myelin oligodendrocyte glycoprotein-induced EAE mice in the acute phase, but not in the chronic phase. During the acute phase of EAE, HS diet intake selectively promoted neutrophil infiltration into the spinal cord without affecting T cell, B cell, and dendritic cell infiltration. The HS diet-induced exacerbation of clinical scores and microglial activation were improved by the pharmacological inhibition of neutrophil chemotaxis with SB225002, a selective CXC chemokine receptor 2 inhibitor. In addition, the pharmacological inhibition of microglial activation with minocycline markedly ameliorated clinical scores of HS diet-fed EAE mice. Compared with normal diet-fed mice, the levels of thrombin (a serine protease involved in microglial activation) and protease activated receptor 1 (PAR-1), a thrombin receptor, were increased in the spinal cords of the HS diet-fed group. Blockade of thrombin signaling with vorapaxar, a selective blocker of PAR-1, significantly improved EAE symptoms in the HS diet group. Collectively, our findings suggest that excessive salt intake promotes EAE induction via the activation of neutrophils and microglia in the spinal cord. Dietary salt restriction might be a promising strategy to prevent developing or relapsing MS.