Animal models of Multiple Sclerosis

Abstract

Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) which involves a complex interaction between immune system and neural cells. Animal modeling has been critical for addressing MS pathogenesis. The three most characterized animal models of MS are (1) the experimental autoimmune/allergic encephalomyelitis (EAE); (2) the virally-induced chronic demyelinating disease, known as Theiler׳s murine encephalomyelitis virus (TMEV) infection and (3) the toxin-induced demyelination. All these models, in a complementary way, have allowed to reach a good knowledge of the pathogenesis of MS. Specifically, EAE is the model which better reflects the autoimmune pathogenesis of MS and is extremely useful to study potential experimental treatments. Furthermore, both TMEV and toxin-induced demyelination models are suitable for characterizing the role of the axonal injury/repair and the remyelination process in MS. In conclusion, animal models, despite their limitations, remain the most useful instrument for implementing the study of MS.

Appearance of claudin-5+ leukocytes in the central nervous system during neuroinflammation: a novel role for endothelial-derived extracellular vesicles

“…Our findings corroborated the presence of CLN-5 + leukocytes in blood during EAE, an animal model of MS [54–56], and further demonstrated their appearance in the CNS. The presence of these cells in both blood and CNS relatively early during disease (D9 EAE) suggests it unlikely they acquire CLN-5 as a consequence of extravasation or only when there is substantial BBB breakdown later in the chronic phase [58, 67].…”

“…To address the issues of whether leukocytes bearing TJ proteins enter the CNS, and the possible origin of these proteins, initial studies were performed to identify leukocytes harboring the TJ protein CLN-5—a determinant of the BBB [53]—in the blood and spinal cord of wild-type mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS [54–56]. EAE was then induced in transgenic mice with eGFP-CLN-5 targeted to endothelial cells to examine if endothelial cells transfer CLN-5 to leukocytes.…”

Immunopathology of Japanese macaque encephalomyelitis is similar to multiple sclerosis

“…Animals presenting with JME possess immunological signatures that are more akin to immunopathogenesis of MS than those of ADEM (Parrish and Yeh, 2012, Wingerchuk and Lucchinetti, 2007, Steiner and Kennedy, 2015). This model has the potential to provide insight into a disease that has proven incredibly difficult to study, as the existing experimentally induced animal models do not recapitulate all aspects of MS (Procaccini et al, 2015). One of the major roadblocks in studying MS directly has been the inability to characterize CNS infiltrating immune cells directly ex vivo .…”

The Gas6/TAM System and Multiple Sclerosis

“…This model allows the study of myelin damage and repair, without the confounding factors of the intense inflammation present in mice with EAE [92,93]. In mice undergoing cuprizone challenge, a change in TAM and Gas6 expression occurs, Tyro3 is down-regulated, while Gas6, Axl, and MerTK transcription are enhanced, paralleling microglial activation.…”