Animal models of multiple sclerosis: applications and future directions in disease research

Multiple sclerosis (MS) is a chronic, inflammatory, and demyelinating disorder of the central nervous system that affects nearly two million individuals worldwide. Characterized by axonal damage, neurodegeneration, and immune-mediated demyelination, MS remains without a cure, and its precise etiology is still unclear. Evidence strongly supports the role of autoimmune mechanisms, with both environmental factors and genetic contributing to disease onset and progression. Animal models have been indispensable in advancing our understanding of MS pathogenesis and in testing therapeutic strategies. Among these, experimental autoimmune encephalomyelitis is the most widely used, closely reproducing immune-mediated inflammation and demyelination. Viral models, such as Theiler's murine encephalomyelitis virus and Semliki Forest virus, provide insights into virus-induced demyelination, while toxin-induced models (e.g., cuprizone and lysolecithin) are valuable for studying demyelination and remyelination processes. Additionally, transgenic and knockout models allow the exploration of specific genetic contributions to disease mechanisms. Despite their limitations no single model fully recapitulates the heterogeneity of MS these approaches remain critical for unraveling disease mechanisms, identifying biomarkers, and developing novel therapeutic interventions. This review highlights the applications and limitations of existing animal models and discusses emerging directions in MS research.