{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:13:45Z","timestamp":1789424025089,"version":"build-2803163510"},"reference-count":82,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammatory demyelination in the central nervous system, predominantly presenting in young adults, with a steadily increasing global incidence. In China, MS is classified as a rare disease and imposes a considerable medical and socioeconomic burden. Current clinical management mainly relies on immunomodulatory and immunosuppressive therapies; however, limitations in long-term efficacy, safety, and economic cost highlight the need for a more comprehensive understanding of disease mechanisms. Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for investigating the immunopathological basis of MS. Although EAE does not fully replicate the heterogeneity and long-term progression of human MS, it provides an important experimental framework for elucidating specific molecular and cellular pathways involved in disease development. This review synthesizes mechanistic evidence derived from EAE studies, focusing on immune regulation, autophagy modulation, gut microbiota-brain axis interactions, maintenance of blood-brain barrier integrity, and inhibition of NLRP3 inflammasome-mediated pyroptosis. By integrating findings within these defined pathological domains, this work aims to clarify how modulation of these interconnected pathways contributes to the present understanding of MS pathogenesis and to discuss their potential clinical relevance. These findings not only enhance our understanding of MS pathogenesis but also provide a foundation for developing multi-target, synergistic therapeutic strategies.<\/jats:p>","DOI":"10.3389\/fnins.2026.1803309","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:00:26Z","timestamp":1777442426000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic insights from experimental autoimmune encephalomyelitis into immune regulation, autophagy, gut microbiota, blood-brain barrier integrity, and NLRP3 inflammasome-mediated pyroptosis in multiple sclerosis: potential clinical implications"],"prefix":"10.3389","volume":"20","author":[{"given":"Shu-Min","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chao","family":"Tang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang-Fei","family":"Liu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian-Qian","family":"Bai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Guo","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Zhi","family":"Bai","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Fei","family":"Wang","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yu","family":"Ma","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun-Ji","family":"Pan","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan-Qin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Fan","sequence":"additional","affiliation":[{"name":"Luoyang Key Laboratory of Neuroimmunology and Innovative Drug Screening","place":["Luoyang, China"]},{"name":"Office of Research & Innovation, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1973834","DOI":"10.1155\/2016\/1973834","article-title":"New insights into the role of oxidative stress mechanisms in the pathophysiology and treatment of multiple sclerosis","volume":"2016","author":"Adamczyk","year":"2016","journal-title":"Oxid. 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