A New Targeted Model of Experimental Autoimmune Encephalomyelitis in the Common Marmoset

Multiple sclerosis (MS) is the most common cause for sustained disability in young adults, yet treatment options remain very limited. Although numerous therapeutic approaches have been effective in rodent models of experimental autoimmune encephalomyelitis (EAE), only few proved to be beneficial in...

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Published inBrain pathology (Zurich, Switzerland) Vol. 26; no. 4; pp. 452 - 464
Main Authors Stassart, Ruth Martha, Helms, Gunther, Garea-Rodríguez, Enrique, Nessler, Stefan, Hayardeny, Liat, Wegner, Christiane, Schlumbohm, Christina, Fuchs, Eberhard, Brück, Wolfgang
Format Journal Article
LanguageEnglish
Published Switzerland Blackwell Publishing Ltd 01.07.2016
John Wiley & Sons, Inc
John Wiley and Sons Inc
Subjects
Animals
Callithrix
common marmoset
Cytokines
Cytokines - administration & dosage
Cytokines - immunology
demyelination
Encephalomyelitis, Autoimmune, Experimental
experimental autoimmune encephalomyelitis
Female
immunomodulation
laquinimod
Male
multiple sclerosis
Myelin-Oligodendrocyte Glycoprotein - administration & dosage
Myelin-Oligodendrocyte Glycoprotein - immunology
Rodents
immunomodulation
experimental autoimmune encephalomyelitis
laquinimod
demyelination
multiple sclerosis
common marmoset
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Summary:Multiple sclerosis (MS) is the most common cause for sustained disability in young adults, yet treatment options remain very limited. Although numerous therapeutic approaches have been effective in rodent models of experimental autoimmune encephalomyelitis (EAE), only few proved to be beneficial in patients with MS. Hence, there is a strong need for more predictive animal models. Within the past decade, EAE in the common marmoset evolved as a potent, alternative model for MS, with immunological and pathological features resembling more closely the human disease. However, an often very rapid and severe disease course hampers its implementation for systematic testing of new treatment strategies. We here developed a new focal model of EAE in the common marmoset, induced by myelin oligodendrocyte glycoprotein (MOG) immunization and stereotactic injections of proinflammatory cytokines. At the injection site of cytokines, confluent inflammatory demyelinating lesions developed that strongly resembled human MS lesions. In a proof‐of‐principle treatment study with the immunomodulatory compound laquinimod, we demonstrate that targeted EAE in marmosets provides a promising and valid tool for preclinical experimental treatment trials in MS research.
Bibliography:istex:3E943F4E27A0BE892242E7F41B46A5F350F26CE0
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Figure S1. A. Marmosets showed no changes in body weight when comparing the day of immunization (day 0) with the end of experiment (day 90). N = 3 per time point, mean, SD, n.s. = non significant. B. Light-microscopic overview demonstrating small, perivascular accentuated lesions (indicated by arrowheads), which were observed in a subset of marmosets with fEAE. LFB-PAS staining, Scale bar 200 μm. C. The total number of cells per area (0.04 mm2) was quantified on light microscopic images and revealed comparable cell densities within demyelinating lesions of human and marmoset. N = 3 per group. Mean, SD, n.s. = non significant. D. Numerous OLIG2 positive cells were detected within demyelinating lesions of fEAE in marmosets. Scale bar 50 μm. Figure S2. A, B. Laquinimod treated animals demonstrate reactive astrocytes at the injection side of cytokines as determined by GFAP immunohistochemistry (A overview, scale bar 200 μm; B higher magnification, scale bar 100 μm). C, D. MRP14 immunohistochemistry reveals a minor microglial reaction to the injection of cytokines in laquinimod treated animals. (C overview, scale bar 200 μm; D higher magnification, scale bar 100 μm).
ArticleID:BPA12292
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:1015-6305
1750-3639
DOI:10.1111/bpa.12292