Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury.

Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury. Research Abstract Details 

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Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury. Abstract Text:

OBJECTIVE: Abnormal myelination is a major pathological sequela of chronic periventricular white matter injury in survivors of premature birth. We tested the hypothesis that myelination failure in chronic hypoxia-ischemia-induced periventricular white matter injury is related to persistent depletion of the oligodendrocyte (OL) precursor pool required to generate mature myelinating OLs. METHODS: A neonatal rat model of hypoxia-ischemia was used where acute degeneration of late OL progenitors (preOLs) occurs via a mostly caspase-independent mechanism. The fate of OL lineage cells in chronic cerebral lesions was defined with OL lineage-specific markers. RESULTS: Acute caspase-3-independent preOL degeneration from hypoxia-ischemia was significantly augmented by delayed preOL death that was caspase-3-dependent. Degeneration of preOLs was offset by a robust regenerative response that resulted in a several-fold expansion in the pool of surviving preOLs in chronic lesions. However, these preOLs displayed persistent maturation arrest with failure to differentiate and generate myelin. When preOL-rich chronic lesions sustained recurrent hypoxia-ischemia at a time in development when white matter is normally resistant to injury, an approximately 10-fold increase in caspase-dependent preOL degeneration occurred relative to lesions caused by a single episode of hypoxia-ischemia. INTERPRETATION: The mechanism of myelination failure in chronic white matter lesions is related to a combination of delayed preOL degeneration and preOL maturation arrest. The persistence of a susceptible population of preOLs renders chronic white matter lesions markedly more vulnerable to recurrent hypoxia-ischemia. These data suggest that preOL maturation arrest may predispose to more severe white matter injury in preterm survivors that sustain recurrent hypoxia-ischemia.

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Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Annals of neurology

VOLUME: 63

Page Numbers: 520-30

Journal Abbreviation: Ann. Neurol.

ISSN: 1531-8249

DAY: 1

MONTH: Apr

YEAR: 2008

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LANGUAGE: eng

NlmUniqueID: 7707449

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Grant and Affiliation Information for Arrested oligodendrocyte lineage maturation in chronic perinatal white matter injury.

AFFILIATION: Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239-3098, USA.

Country: United States

AGENCY: United States NINDS

GRANT: R37NS045737

ACRONYM: NS

MEDLINETA: Ann Neurol

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