Preferential loss of myelin-associated glycoprotein reflects hypoxia-like white matter damage in stroke and inflammatory brain diseases

Fahmy Aboul-Enein, Helmut Rauschka, Barbara Kornek, Christine Stadelmann, Andreas Stefferl, Wolfgang Brück, Claudia Lucchinetti, Manfred Schmidbauer, Kurt Jellinger, Hans Lassmann

Research output: Contribution to journalArticle

218 Scopus citations

Abstract

Destruction of myelin and oligodendrocytes leading to the formation of large demyelinated plaques is the hallmark of multiple sclerosis (MS) pathology. In a subset of MS patients termed pattern III, actively demyelinating lesions show preferential loss of myelin-associated glycoprotein (MAG) and apoptotic-like oligodendrocyte destruction, whereas other myelin proteins remain well preserved. MAG is located in the most distal periaxonal oligodendrocyte processes and primary "dying back" oligodendrogliopathy may be the initial step of myelin degeneration in pattern III lesions. In the present study, various human white matter pathologies, including acute and chronic white matter stroke, virus encephalitis, metabolic encephalopathy, and MS were studied. In addition to a subset of MS cases, a similar pattern of demyelination was found in some cases of virus encephalitis as well as in all lesions of acute white matter stroke. Brain white matter lesions presenting with MAG loss and apoptotic-like oligodendrocyte destruction, irrespective of their primary disease cause, revealed a prominent nuclear expression of hypoxia inducible factor-1α in various cell types, including oligodendrocytes. Our data suggest that a hypoxia-like tissue injury may play a pathogenetic role in a subset of inflammatory demyelinating brain lesions.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number1
DOIs
StatePublished - Jan 1 2003

Keywords

  • Brain hypoxia
  • HIF-I
  • Multiple sclerosis
  • Myelin-associated glycoprotein
  • Virus encephalitis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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