Animal model of multiple sclerosis: Experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a very complex and heterogeneous disease, with an unknown etiology and which, currently, remains incurable. For this reason, animal models are crucial to investigate this disease, which has increased in prevalence in recent years, affecting 2.8 million people worldwide, and is the leading cause of non-traumatic disability in young adults between the ages of 20-30years. Of all the models developed to replicate MS, experimental autoimmune encephalomyelitis (EAE) best reflects the autoimmune pathogenesis of MS. There are different methods to induce it, which will give rise to different types of EAE, which will vary in clinical presentation and severity. Of the EAE models, the most widespread and used is the one induced in rodents due to its advantages over other species. Likewise, EAE has become a widely used model in the development of therapies for the treatment of MS. Likewise, it is very useful to define the cellular and molecular mechanisms involved in the pathogenesis of MS and to establish therapeutic targets for this disease. For all these reasons, the EAE model plays a key role in improving the understanding of MS.

Muñoz-Jurado A ，Escribano BM ，Túnez I 《Methods in Cell Biology》

Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair.

While many groups use experimental autoimmune encephalomyelitis (EAE) as a model to uncover therapeutic targets and understand the pathology underlying multiple sclerosis (MS), EAE protocol variability introduces discrepancies in central nervous system (CNS) pathogenesis and clinical disease, limiting the comparability between studies and slowing much-needed translational research. Here we describe a detailed, reliable protocol for chronic EAE induction in C57BL/6 mice utilizing two injections of myelin oligodendrocyte glycoprotein (35-55) peptide mixed with complete Freund's adjuvant and paired with pertussis toxin. The active MOG35-55-EAE protocol presented here induces ascending paralysis in 80-100% of immunized mice. We observe: (1) consistent T cell immune activation, (2) robust CNS infiltration by peripheral immune cells, and (3) perivascular demyelinating lesions concurrent with axon damage in the spinal cord and various brain regions, including the optic nerve, cortex, hippocampus, internal capsule, and cerebellum. Lack of detailed protocols, combined with variability between laboratories, make EAE results difficult to compare and hinder the use of this model for therapeutic development. We provide the most detailed active MOG35-55-EAE protocol to date. With this protocol, we observe high disease incidence and a consistent, reliable disease course. The resulting pathology is MS-like and includes optic neuritis, perivascular mononuclear infiltration, CNS axon demyelination, and axon damage in both infiltrating lesions and otherwise normal-appearing white matter. By providing a detailed active MOG35-55-EAE protocol that yields consistent and robust pathology, we aim to foster comparability between pre-clinical studies and facilitate the discovery of MS therapeutics.

Hasselmann JPC ，Karim H ，Khalaj AJ ，Ghosh S ，Tiwari-Woodruff SK ... -  《-》

Animal models of multiple sclerosis: Focus on experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic, progressive disorder of the central nervous system (CNS) that affects more than two million people worldwide. Several animal models resemble MS pathology; the most employed are experimental autoimmune encephalomyelitis (EAE) and toxin- and/or virus-induced demyelination. In this review we will summarize our knowledge on the utility of different animal models in MS research. Although animal models cannot replicate the complexity and heterogeneity of the MS pathology, they have proved to be useful for the development of several drugs approved for treatment of MS patients. This review focuses on EAE because it represents both clinical and pathological features of MS. During the past decades, EAE has been effective in illuminating various pathological processes that occur during MS, including inflammation, CNS penetration, demyelination, axonopathy, and neuron loss mediated by immune cells.

Bjelobaba I ，Begovic-Kupresanin V ，Pekovic S ，Lavrnja I ... -  《-》

Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS).

Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination, axonal loss and gliosis. The counter-regulatory mechanisms of resolution of inflammation and remyelination also occur in EAE, which, therefore can also serve as a model for these processes. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are in current or imminent use in MS have been developed, tested or validated on the basis of EAE studies. There is great heterogeneity in the susceptibility to the induction, the method of induction and the response to various immunological or neuropharmacological interventions, many of which are reviewed here. This makes EAE a very versatile system to use in translational neuro- and immunopharmacology, but the model needs to be tailored to the scientific question being asked. While creating difficulties and underscoring the inherent weaknesses of this model of MS in straightforward translation from EAE to the human disease, this variability also creates an opportunity to explore multiple facets of the immune and neural mechanisms of immune-mediated neuroinflammation and demyelination as well as intrinsic protective mechanisms. This allows the eventual development and preclinical testing of a wide range of potential therapeutic interventions.

Constantinescu CS ，Farooqi N ，O'Brien K ，Gran B ... -  《-》

Enhancing the ability of experimental autoimmune encephalomyelitis to serve as a more rigorous model of multiple sclerosis through refinement of the experimental design.

Emerson MR ，Gallagher RJ ，Marquis JG ，LeVine SM ... -  《COMPARATIVE MEDICINE》