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Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons

Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leukocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS lesion...

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Autores principales: Singh, Shailender, Metz, Imke, Amor, Sandra, van der Valk, Paul, Stadelmann, Christine, Brück, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer-Verlag 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611040/
https://www.ncbi.nlm.nih.gov/pubmed/23354834
http://dx.doi.org/10.1007/s00401-013-1082-0
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author Singh, Shailender
Metz, Imke
Amor, Sandra
van der Valk, Paul
Stadelmann, Christine
Brück, Wolfgang
author_facet Singh, Shailender
Metz, Imke
Amor, Sandra
van der Valk, Paul
Stadelmann, Christine
Brück, Wolfgang
author_sort Singh, Shailender
collection PubMed
description Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leukocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS lesions. Although the etiology of MS is still not known, inflammation and autoimmunity are considered to be the central components of this disease. Previous studies provide evidence that Wallerian degeneration, occurring as a consequence of structural damage in MS lesions, might be responsible for observed pathological abnormalities in connected normal-appearing white matter. As innate immune cells, microglia/macrophages are the first to react to even minor pathological changes in the CNS. Biopsy tissue from 27 MS patients and autopsy and biopsy tissue from 22 normal and pathological controls were analyzed to determine the incidence of microglial nodules. We assessed MS periplaque white matter tissue from early disease stages to determine whether microglial nodules are associated with altered axons. With immunohistochemical methods, the spatial relation of the two phenomena was visualized using HLA-DR antibody for MHC II expression by activated microglia/macrophages and by applying antibodies against damaged axons, i.e., SMI32 (non-phosphorylated neurofilaments) and amyloid precursor protein as well as neuropeptide Y receptor Y1, which marks axons undergoing Wallerian degeneration. Our data demonstrate that the occurrence of microglial nodules is not specific to MS and is associated with degenerating as well as damaged axons in early MS. In addition, we show that early MS microglial nodules exhibit both pro- and antiinflammatory phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-013-1082-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-36110402013-04-01 Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons Singh, Shailender Metz, Imke Amor, Sandra van der Valk, Paul Stadelmann, Christine Brück, Wolfgang Acta Neuropathol Original Paper Microglial nodules in the normal-appearing white matter have been suggested as the earliest stage(s) of multiple sclerosis (MS) lesion formation. Such nodules are characterized by an absence of leukocyte infiltration, astrogliosis or demyelination, and may develop into active demyelinating MS lesions. Although the etiology of MS is still not known, inflammation and autoimmunity are considered to be the central components of this disease. Previous studies provide evidence that Wallerian degeneration, occurring as a consequence of structural damage in MS lesions, might be responsible for observed pathological abnormalities in connected normal-appearing white matter. As innate immune cells, microglia/macrophages are the first to react to even minor pathological changes in the CNS. Biopsy tissue from 27 MS patients and autopsy and biopsy tissue from 22 normal and pathological controls were analyzed to determine the incidence of microglial nodules. We assessed MS periplaque white matter tissue from early disease stages to determine whether microglial nodules are associated with altered axons. With immunohistochemical methods, the spatial relation of the two phenomena was visualized using HLA-DR antibody for MHC II expression by activated microglia/macrophages and by applying antibodies against damaged axons, i.e., SMI32 (non-phosphorylated neurofilaments) and amyloid precursor protein as well as neuropeptide Y receptor Y1, which marks axons undergoing Wallerian degeneration. Our data demonstrate that the occurrence of microglial nodules is not specific to MS and is associated with degenerating as well as damaged axons in early MS. In addition, we show that early MS microglial nodules exhibit both pro- and antiinflammatory phenotypes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00401-013-1082-0) contains supplementary material, which is available to authorized users. Springer-Verlag 2013-01-26 2013 /pmc/articles/PMC3611040/ /pubmed/23354834 http://dx.doi.org/10.1007/s00401-013-1082-0 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by/2.0/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Paper
Singh, Shailender
Metz, Imke
Amor, Sandra
van der Valk, Paul
Stadelmann, Christine
Brück, Wolfgang
Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
title Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
title_full Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
title_fullStr Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
title_full_unstemmed Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
title_short Microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
title_sort microglial nodules in early multiple sclerosis white matter are associated with degenerating axons
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3611040/
https://www.ncbi.nlm.nih.gov/pubmed/23354834
http://dx.doi.org/10.1007/s00401-013-1082-0
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