Cellular and molecular pathogenesis of periventricular white matter injury

Stephen A. Back, Joseph J. Volpe

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Periventricular white matter injury has a high incidence, particularly in the premature infant. A prominent feature of the pathogenesis of this injury, which ultimately results in disrupted myelination of periventricular white matter tracts, is a loss of oligodendrocytes (OLs). The timing of injury corresponds to the period in white matter development when OL precursors predominate. This article focuses on current understanding of the cellular and molecular basis for the developmental vulnerability of OL precursors that may predispose to their loss in periventricular leukomalacia (PVL). Recent advances in the cellular neurobiology of OL development have permitted study of the processes that regulate survival of developing OLs. Several potentially complementary etiologies for the developmental vulnerability of OL precursors are reviewed: (1) free-radical-mediated toxicity in the setting of oxidative stress, (2) cytotoxic cytokines, and (3) a critical dependence on selected trophic factors during certain periods in OL development. Recent work indicates that these causes of cell death are mediated by a common mechanism involving apoptosis. Potential therapeutic interventions for interruption of the pathways mediating OL death are examined.

Original languageEnglish (US)
Pages (from-to)96-107
Number of pages12
JournalMental Retardation and Developmental Disabilities Research Reviews
Volume3
Issue number1
DOIs
StatePublished - Jan 1 1997

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Keywords

  • antioxidant enzymes
  • apoptosis
  • cytokine
  • development
  • glutamate
  • glutathione
  • growth factor
  • iron
  • oligodendrocyte
  • oxygen free radicals
  • periventricular leukomalacia

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Neuropsychology and Physiological Psychology
  • Genetics(clinical)

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