Disease-specific molecular events in cortical multiple sclerosis lesions

Marie Therese Fischer, Isabella Wimmer, Romana Höftberger, Susanna Gerlach, Lukas Haider, Tobias Zrzavy, Simon Hametner, Don Mahad, Christoph J Binder, Markus Krumbholz, Jan Bauer, Monika Bradl, Hans Lassmann

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)1799-815
Number of pages17
JournalBrain
Volume136
Issue numberPt 6
DOIs
Publication statusPublished - Jun 2013

Keywords / Materials (for Non-textual outputs)

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cerebral Cortex
  • Female
  • Humans
  • Inflammation Mediators
  • Male
  • Middle Aged
  • Multiple Sclerosis
  • Oxidative Stress
  • Protein Array Analysis
  • Young Adult

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