Journal Article10.1038/NN738
TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination.
Heather A. Arnett,Jeffrey B. Mason,Jeffrey B. Mason,Mike Marino,Kinuko Suzuki,Glenn K. Matsushima,Jenny P.-Y. Ting +6 more
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TL;DR: Analysis of mice lacking TNF receptor 1 (TNFR1) or TNFR2 indicated thatTNFR2, not TNFR1, is critical to oligodendrocyte regeneration, and this unexpected reparative role for TNFα in the CNS is important for understanding oligod endocrine regeneration/proliferation, nerve remyelination and the design of new therapeutics for demyelinating diseases.
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Abstract: Here we used mice lacking tumor necrosis factor-alpha (TNF alpha) and its associated receptors to study a model of demyelination and remyelination in which these events could be carefully controlled using a toxin, cuprizone. Unexpectedly, the lack of TNF alpha led to a significant delay in remyelination as assessed by histology, immunohistochemistry for myelin proteins and electron microscopy coupled with morphometric analysis. Failure of repair correlated with a reduction in the pool of proliferating oligodendrocyte progenitors (bromodeoxyuridine-labeled NG2(+) cells) followed by a reduction in the number of mature oligodendrocytes. Analysis of mice lacking TNF receptor 1 (TNFR1) or TNFR2 indicated that TNFR2, not TNFR1, is critical to oligodendrocyte regeneration. This unexpected reparative role for TNF alpha in the CNS is important for understanding oligodendrocyte regeneration/proliferation, nerve remyelination and the design of new therapeutics for demyelinating diseases.
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References
The TNF and TNF receptor superfamilies: integrating mammalian biology.
TL;DR: The authors regret the inability to cite all of the primary literature contributing to this review due to length considerations, but wish to thank F. Chan, T. Migone, and J. Wang for insightful comments on the manuscript.
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Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response.
TL;DR: A physiological role for TNF alpha in regulating the development and organization of splenic follicular architecture and in the maturation of the humoral immune response is established.
The Neurotoxicant, Cuprizone, as a Model to Study Demyelination and Remyelination in the Central Nervous System
TL;DR: The reproducibility of the model indicates that it may allow for testing of manipulations which may accelerate or repress the process of demyelination and or remyelinated areas, and which can be tested more rigorously with the cuprizone model.
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•Journal Article
TNF neutralization in MS - Results of a randomized, placebo-controlled multicenter study
Arnason Bgw.,G Jacobs,M Hanlon,B H Clay,Noronha Abc.,A Auty,B Davis,Avindra Nath,Jean-Pierre Bouchard,C Belanger,F Gosselin,Manon Thibault,Pierre Duquette,P Bourgoin,Rebecca M. DuBois,M. Girard,George C. Ebers,Rice Gpa.,Margaret K. Vandervoort,Gordon S. Francis,L Duncan,Yves Lapierre,M. S. Freedman,S N Christie,Hyman Rabinovitch,David G. Patry,W F Murphy,S Peters,S D McGuiness,T J Murray,Virender Bhan,Charles Maxner,R. A. Van Dorpe,J J Oger,J. Nelson,W. Morrison,N Bogle,S Beall,G Vorobeychick,A V Hiltbrunner,J Bock,W Lesslauer,Li Dkb.,Donald W. Paty,Guojun Zhao,Grp Lmss.,Grp Ubcmsmria. +46 more
TL;DR: Lenercept failed to be beneficial, but insight into the role of TNF in MS exacerbations was gained.
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Identification of autoantibodies associated with myelin damage in multiple sclerosis
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