The use of animal models to investigate the pathogenesis of neuroinflammatory disorders of the central nervous system.

Abstract

A major hurdle in the research of neuroinflammatory disorders of the central nervous system is the inaccessibility of the organ. Thus investigation is limited to end-stage disease and systemic changes that occur during disease progression, neither of which may reflect the pathological process in the central nervous system. These factors may explain the lack of effective therapies in multiple sclerosis, a common chronic inflammatory disease of the central nervous system. To overcome such limitations approaches using more relevant animal models have been developed to study pathological mechanisms as well as the design of rational therapeutic strategies. This review describes the animal models used to study pathological processes leading to inflammation within the central nervous system that may be operating in multiple sclerosis and the use of these models in the design of more rational therapeutic strategies. The clinical heterogeneity of multiple sclerosis as well as the finding of different pathological patterns suggests that multiple sclerosis may be a spectrum of diseases that may represent different pathological processes. This and the renewed interest in the extent of axonal damage has led to the development of more relevant animal models, such as those in nonhuman primates, that both reflect the spectrum of multiple sclerosis and allow the development of species-specific therapeutic approaches. While many animal models are available, the use of relevant animal models that mimic either the different forms of multiple sclerosis or the spectrum of multiple sclerosis is critical to examine those factors, for example genes or proteins, that are of pathogenic relevance and can be used as targets for therapy.