title: Disease-specific molecular events in cortical multiple sclerosis lesions.
abstract: 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.
authors.affiliation: Department of Neuroimmunology, Centre for Brain Research, Medical University of Vienna, Austria.
authors.forename: Marie Therese
authors.initials: MT
authors.lastname: Fischer
authors.forename: Isabella
authors.initials: I
authors.lastname: Wimmer
authors.forename: Romana
authors.initials: R
authors.lastname: Höftberger
authors.forename: Susanna
authors.initials: S
authors.lastname: Gerlach
authors.forename: Lukas
authors.initials: L
authors.lastname: Haider
authors.forename: Tobias
authors.initials: T
authors.lastname: Zrzavy
authors.forename: Simon
authors.initials: S
authors.lastname: Hametner
authors.forename: Don
authors.initials: D
authors.lastname: Mahad
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.forename: Markus
authors.initials: M
authors.lastname: Krumbholz
authors.forename: Jan
authors.initials: J
authors.lastname: Bauer
authors.forename: Monika
authors.initials: M
authors.lastname: Bradl
authors.forename: Hans
authors.initials: H
authors.lastname: Lassmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002540:Cerebral Cortex / Q000473:pathology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology; D040081:Protein Array Analysis / Q000379:methods; D055815:Young Adult
chemical_list: D018836:Inflammation Mediators
keywords: cortex; demyelination; gene expression; multiple sclerosis; neurodegeneration