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Pathogenic processes underlying diseases in humans and dogs are similar or identical, which exemplifies the One Health concept. Companion animals share physiological and genetic traits with humans, have similar exposure to microorganisms and toxic insults, and due to cohabitation, share our microbiome. Dogs have intact immune systems and tolerate drugs at dosages comparable to humans. Dogs with naturally occurring neuroinflammatory disorders can serve as spontaneous models for those affecting humans. Granulomatous meningoencephalomyelitis, the most common canine neuroinflammatory disorder, recapitulates key immunopathological features of multiple sclerosis. The clinical course of granulomatous meningoencephalomyelitis is prolonged from months to years, rather than days to weeks as in rodents, a key aspect when modeling multiple sclerosis chronicity and assessing drug response over time. Thus, establishing natural models of human diseases constitutes a significant advancement to understanding mechanisms of disease while benefiting veterinary medicine and accelerating new therapies for humans.<\/jats:p>","DOI":"10.1093\/jimmun\/vkaf236","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T08:01:31Z","timestamp":1761897691000},"page":"2535-2542","source":"Crossref","is-referenced-by-count":1,"title":["Neuroinflammatory canine disorders: unveiling disease mechanisms from a One Health perspective"],"prefix":"10.1093","volume":"214","author":[{"given":"Molly E","family":"Church","sequence":"first","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara I","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8216-5129","authenticated-orcid":false,"given":"Jorge I","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"2025103104011988200_vkaf236-B1","doi-asserted-by":"crossref","first-page":"108484","DOI":"10.1016\/j.jneumeth.2019.108484","article-title":"Companion animal models of neurological disease","volume":"331","author":"Partridge","year":"2020","journal-title":"J Neurosci Methods"},{"key":"2025103104011988200_vkaf236-B2","doi-asserted-by":"crossref","first-page":"44","DOI":"10.4049\/jimmunol.2000514","article-title":"Meningeal B cell clusters correlate with submeningeal pathology in a natural model of multiple sclerosis","volume":"207","author":"Church","year":"2021","journal-title":"J Immunol"},{"key":"2025103104011988200_vkaf236-B3","doi-asserted-by":"crossref","DOI":"10.2460\/ajvr.23.07.0164","article-title":"An early clinical phenotype of necrotizing meningoencephalitis in the pug reveals similarities to multiple sclerosis in humans","volume":"85","author":"Windsor","year":"2024","journal-title":"Am J Vet Res"},{"key":"2025103104011988200_vkaf236-B4","doi-asserted-by":"crossref","first-page":"1465689","DOI":"10.3389\/fvets.2024.1465689","article-title":"Of potential new treatment targets and polythetic approach in meningoencephalitis of unknown origin: a review","volume":"11","author":"Nessler","year":"2024","journal-title":"Front Vet Sci"},{"key":"2025103104011988200_vkaf236-B5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.tvjl.2018.12.007","article-title":"Clinical presentation, diagnostic findings, prognostic factors, treatment and outcome in dogs with meningoencephalomyelitis of unknown origin: a review","volume":"244","author":"Cornelis","year":"2019","journal-title":"Vet J"},{"key":"2025103104011988200_vkaf236-B6","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/S1474-4422(23)00148-5","article-title":"Differential diagnosis of suspected multiple sclerosis: an updated consensus approach","volume":"22","author":"Solomon","year":"2023","journal-title":"Lancet Neurol"},{"key":"2025103104011988200_vkaf236-B7","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1053\/j.tcam.2018.11.003","article-title":"Immune-mediated central nervous system disease\u2014current knowledge and recommendations","volume":"34","author":"Vitale","year":"2019","journal-title":"Top Companion Anim Med"},{"key":"2025103104011988200_vkaf236-B8","first-page":"178","article-title":"Neuroinflammatory diseases of the central nervous system of dogs: a retrospective study of 207 cases (2008\u20132019)","volume":"63","author":"Elbert","year":"2022","journal-title":"Can Vet J"},{"key":"2025103104011988200_vkaf236-B9","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3389\/fvets.2019.00286","article-title":"Glioma mimics: magnetic resonance imaging characteristics of granulomas in dogs","volume":"6","author":"Diangelo","year":"2019","journal-title":"Front Vet Sci"},{"key":"2025103104011988200_vkaf236-B10","doi-asserted-by":"crossref","first-page":"105678","DOI":"10.1016\/j.tvjl.2021.105678","article-title":"Biomarkers of non-infectious inflammatory CNS diseases in dogs\u2014where are we now? 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