Disease-specific molecular events in cortical multiple sclerosis lesions

Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene express...

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Published in:Brain (London, England : 1878) Vol. 136; no. Pt 6; p. 1799
Main Authors: Fischer, Marie Therese, Wimmer, Isabella, Höftberger, Romana, Gerlach, Susanna, Haider, Lukas, Zrzavy, Tobias, Hametner, Simon, Mahad, Don, Binder, Christoph J, Krumbholz, Markus, Bauer, Jan, Bradl, Monika, Lassmann, Hans
Format: Journal Article
Language:English
Published: England 01.06.2013
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Cerebral Cortex - pathology
Female
Humans
Inflammation Mediators - physiology
Male
Middle Aged
Multiple Sclerosis - genetics
Multiple Sclerosis - pathology
Oxidative Stress - physiology
Protein Array Analysis - methods
Young Adult
cortex
neurodegeneration
demyelination
multiple sclerosis
gene expression
ISSN:1460-2156, 1460-2156
Online Access:Get more information
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Summary:Cortical lesions constitute an important part of multiple sclerosis pathology. Although inflammation appears to play a role in their formation, the mechanisms leading to demyelination and neurodegeneration are poorly understood. We aimed to identify some of these mechanisms by combining gene expression studies with neuropathological analysis. In our study, we showed that the combination of inflammation, plaque-like primary demyelination and neurodegeneration in the cortex is specific for multiple sclerosis and is not seen in other chronic inflammatory diseases mediated by CD8-positive T cells (Rasmussen's encephalitis), B cells (B cell lymphoma) or complex chronic inflammation (tuberculous meningitis, luetic meningitis or chronic purulent meningitis). In addition, we performed genome-wide microarray analysis comparing micro-dissected active cortical multiple sclerosis lesions with those of tuberculous meningitis (inflammatory control), Alzheimer's disease (neurodegenerative control) and with cortices of age-matched controls. More than 80% of the identified multiple sclerosis-specific genes were related to T cell-mediated inflammation, microglia activation, oxidative injury, DNA damage and repair, remyelination and regenerative processes. Finally, we confirmed by immunohistochemistry that oxidative damage in cortical multiple sclerosis lesions is associated with oligodendrocyte and neuronal injury, the latter also affecting axons and dendrites. Our study provides new insights into the complex mechanisms of neurodegeneration and regeneration in the cortex of patients with multiple sclerosis.
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ISSN:1460-2156
1460-2156
DOI:10.1093/brain/awt110