Document Detail

The developing oligodendrocyte: key cellular target in brain injury in the premature infant.
MedLine Citation:
PMID:  21382469     Owner:  NLM     Status:  MEDLINE    
Brain injury in the premature infant, a problem of enormous importance, is associated with a high risk of neurodevelopmental disability. The major type of injury involves cerebral white matter and the principal cellular target is the developing oligodendrocyte. The specific phase of the oligodendroglial lineage affected has been defined from study of both human brain and experimental models. This premyelinating cell (pre-OL) is vulnerable because of a series of maturation-dependent events. The pathogenesis of pre-OL injury relates to operation of two upstream mechanisms, hypoxia-ischemia and systemic infection/inflammation, both of which are common occurrences in premature infants. The focus of this review and of our research over the past 15-20 years has been the cellular and molecular bases for the maturation-dependent vulnerability of the pre-OL to the action of the two upstream mechanisms. Three downstream mechanisms have been identified, i.e., microglial activation, excitotoxicity and free radical attack. The work in both experimental models and human brain has identified a remarkable confluence of maturation-dependent factors that render the pre-OL so exquisitely vulnerable to these downstream mechanisms. Most importantly, elucidation of these factors has led to delineation of a series of potential therapeutic interventions, which in experimental models show marked protective properties. The critical next step, i.e., clinical trials in the living infant, is now on the horizon.
Joseph J Volpe; Hannah C Kinney; Frances E Jensen; Paul A Rosenberg
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2011-03-05
Journal Detail:
Title:  International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience     Volume:  29     ISSN:  1873-474X     ISO Abbreviation:  Int. J. Dev. Neurosci.     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-05-16     Completed Date:  2011-09-13     Revised Date:  2013-10-28    
Medline Journal Info:
Nlm Unique ID:  8401784     Medline TA:  Int J Dev Neurosci     Country:  England    
Other Details:
Languages:  eng     Pagination:  423-40     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.
Department of Neurology, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.
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MeSH Terms
Brain Injuries / etiology,  pathology*,  physiopathology
Glutamic Acid / toxicity
Hypoxia-Ischemia, Brain / complications,  pathology,  physiopathology
Immunity, Innate
Infant, Newborn
Infant, Premature
Infant, Premature, Diseases / pathology*,  physiopathology
Leukomalacia, Periventricular / complications,  pathology,  physiopathology
Microglia / physiology
Oligodendroglia / cytology,  pathology*,  physiology*
Reactive Oxygen Species / metabolism
Grant Support
Reg. No./Substance:
0/Reactive Oxygen Species; 56-86-0/Glutamic Acid
Republished in:
Int J Dev Neurosci. 2011 Oct;29(6):565-82   [PMID:  21802506 ]

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