title: Focal necrosis and disturbed myelination in the white matter of newborn infants: a tale of too much or too little oxygen.
abstract: White matter disease in preterm infants comes along with focal destructions or with diffuse myelination disturbance. Recent experimental work with transgenic mice paves the way for a unifying molecular model for both types of brain injury, placing oxygen sensing by oligodendrocyte precursor cells (OPCs) at the center stage. Mice genetically altered to mimic high local oxygen tension in oligodendroglia lineage cells (via deletion of hypoxia-inducible factor, HIF) develop white matter disease resembling cystic periventricular leukomalacia within the first 7 days of life. Mice in which local hypoxia is mimicked in oligodendroglial cells (via genetic inhibition of HIF decay) display arrested OPC maturation and subsequent hypomyelination, reminiscent of the diffuse white matter disease observed in preterm infants and infants with congenital heart disease. These recent experimental findings on oxygen sensing and myelination are awaiting integration into a clinical framework. Gene regulation in response to hyperoxia or hypoxia, rather than oxidative stress, may be an important mechanism underlying neonatal white matter disease.
authors: Division of Neonatology, University Children's Hospital , Basel , Switzerland.
authors: Sven
authors: S
authors: Wellmann
authors: Department of Neonatology, Charité University Medical Center , Berlin , Germany.
authors: Christoph
authors: C
authors: Bührer
authors: Department of Neonatology, Charité University Medical Center , Berlin , Germany.
authors: Thomas
authors: T
authors: Schmitz
keywords: hypoxia-inducible factor; myelination; oligodendrocyte precursors; periventricular leukomalacia; white matter disease
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