Neuroinflammatory canine disorders: unveiling disease mechanisms from a One Health perspective.

While rodent models remain foundational in biomedical research for their manipulability, genetics, and reproducibility, spontaneous diseases in companion animals provide relevant models to study naturally occurring conditions. 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.