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

J Neuropathol Exp Neurol. 2003 Jan;62(1):25-33. doi: 10.1093/jnen/62.1.25.

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-1alpha 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Brain Diseases / metabolism
  • Brain Diseases / pathology
  • Child
  • Encephalitis / metabolism*
  • Encephalitis / pathology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Hypoxia-Ischemia, Brain / metabolism*
  • Hypoxia-Ischemia, Brain / pathology
  • Middle Aged
  • Myelin-Associated Glycoprotein / analysis
  • Myelin-Associated Glycoprotein / metabolism*
  • Oligodendroglia / chemistry
  • Oligodendroglia / metabolism*
  • Oligodendroglia / pathology
  • Stroke / metabolism*
  • Stroke / pathology
  • Transcription Factors / biosynthesis

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Myelin-Associated Glycoprotein
  • Transcription Factors