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

Abstract

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.

Figure 1

Schematic diagram of some of the key pathological features of EAE pathogenesis. Activated Th1 cells and Th17 cells are thought to be the main culprit in EAE and MS. Th1 are IFN-γ producing, and Th17 are IL-17 producing T lymphocytes. They are primed outside the CNS by dendritic cells, then cross the blood–brain barrier and encounter CNS antigen-presenting cells. They produce inflammatory products and cytokines that damage the myelin and axons. They also activate the resident microglia and produce factors that attract further inflammatory cells to the CNS and perpetuate the inflammatory cascade. Antibodies and B cells can also enter the CNS, and plasma cells produce antibodies within the CNS. Antibody mediated damage contributes to the inflammatory demyelination and neurodegeneration.