{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T11:52:52Z","timestamp":1789559572184,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,9,23]],"date-time":"2013-09-23T00:00:00Z","timestamp":1379894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2013,11]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Therapeutic strategies that induce effective neuroprotection and enhance intrinsic repair mechanisms are central goals for future treatment of multiple sclerosis (MS<\/jats:styled-content>), as well as other diseases. Laquinimod (LQ<\/jats:styled-content>) is an orally administered, central nervous system (CNS<\/jats:styled-content>)\u2010active immunomodulator with demonstrated efficacy in MS<\/jats:styled-content> clinical trials and a favorable safety and tolerability profile.<\/jats:p><\/jats:sec>Aims<\/jats:title>We aimed to explore the pathological, functional, and behavioral consequences of prophylactic and therapeutic (after presentation of peak clinical disease) LQ<\/jats:styled-content> treatment in the chronic experimental autoimmune encephalomyelitis (EAE<\/jats:styled-content>) mouse model of MS<\/jats:styled-content>.<\/jats:p><\/jats:sec>Materials and methods<\/jats:title>Active EAE<\/jats:styled-content>\u2010induced 8\u2010week\u2010old C57BL<\/jats:styled-content>\/6 mice were treated with 5 or 25 mg\/kg\/day LQ<\/jats:styled-content> via oral gavage beginning on EAE<\/jats:styled-content> post\u2010immunization day 0, 8, or 21. Clinical scores and rotorod motor performance were assessed throughout the disease course. Immune analysis of autoantigen\u2010stimulated splenocytes, electrophysiological conduction of callosal axons, and immunohistochemistry of white matter\u2010rich corpus callosum and spinal cord were performed.<\/jats:p><\/jats:sec>Results<\/jats:title>Prophylactic and therapeutic treatment with LQ<\/jats:styled-content> significantly decreased mean clinical disease scores, inhibited Th1 cytokine production, and decreased the CNS<\/jats:styled-content> inflammatory response. LQ<\/jats:styled-content>\u2010induced improvement in axon myelination and integrity during EAE<\/jats:styled-content> was functional, as evidenced by significant recovery of callosal axon conduction and axon refractoriness and pronounced improvement in rotorod motor performance. These improvements correlate with LQ<\/jats:styled-content>\u2010induced attenuation of EAE<\/jats:styled-content>\u2010induced demyelination and axon damage, and improved myelinated axon numbers.<\/jats:p><\/jats:sec>Discussion<\/jats:title>Even when initiated at peak disease, LQ<\/jats:styled-content> treatment has beneficial effects within the chronic EAE<\/jats:styled-content> mouse model. In addition to its immunomodulatory effects, the positive effects of LQ<\/jats:styled-content> treatment on oligodendrocyte numbers and myelin density are indicative of significant, functional neuroprotective and neurorestorative effects.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Our results support a potential neuroprotective, in addition to immunomodulatory, effect of LQ<\/jats:styled-content> treatment in inhibiting ongoing MS<\/jats:styled-content>\/EAE<\/jats:styled-content> disease progression.<\/jats:p><\/jats:sec>","DOI":"10.1002\/brb3.174","type":"journal-article","created":{"date-parts":[[2013,10,11]],"date-time":"2013-10-11T22:03:28Z","timestamp":1381529008000},"page":"664-682","source":"Crossref","is-referenced-by-count":40,"title":["Therapeutic laquinimod treatment decreases inflammation, initiates axon remyelination, and improves motor deficit in a mouse model of multiple 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