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The underlying multifactorial anti\u2010inflammatory, neuroprotective effect of GA is in the induction of reactive T cells that release immunomodulatory cytokines and neurotrophic factors at the injury site. These GA\u2010induced cytokines and growth factors may have a direct effect on axon function. Building on previous findings that suggest a neuroprotective effect of GA, we assessed the therapeutic effects of GA on brain and spinal cord pathology and functional correlates using the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Therapeutic regimens were utilized based on promising prophylactic efficacy. More specifically, C57BL\/6 mice were treated with 2 mg\/mouse\/day GA for 8 days beginning at various time points after EAE post\u2010induction day 15, yielding a thorough, clinically relevant assessment of GA efficacy within the context of severe progressive disease. Therapeutic treatment with GA significantly decreased clinical scores and improved rotorod motor performance in EAE mice. These functional improvements were supported by an increase in myelinated axons and fewer amyloid precursor protein\u2010positive axons in the spinal cords of GA\u2010treated EAE mice. Furthermore, therapeutic GA decreased microglia\/macrophage and T cell infiltrates and increased oligodendrocyte numbers in both the spinal cord and corpus callosum of EAE mice. Finally, GA improved callosal axon conduction and nodal protein organization in EAE. Our results demonstrate that therapeutic GA treatment has significant beneficial effects in a chronic mouse model of MS, in which its positive effects on both myelinated and non\u2010myelinated axons results in improved axon function. \u00a9 2014 The Authors. 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