Reprint of "The developing oligodendrocyte: key cellular target in brain injury in the premature infant"

被引:51
作者
Volpe, Joseph J. [1 ,2 ]
Kinney, Hannah C. [2 ,3 ]
Jensen, Frances E. [1 ,2 ]
Rosenberg, Paul A. [1 ,2 ]
机构
[1] Childrens Hosp, Dept Neurol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA
关键词
Developing oligodendrocyte; Excitotoxicity; Free radicals; Hypoxia-ischemia; Microglial activation; Premature brain injury; WHITE-MATTER INJURY; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; INTRACELLULAR ZINC RELEASE; NEONATAL HYPOXIA-ISCHEMIA; DEVELOPING RAT-BRAIN; DOSE RECOMBINANT ERYTHROPOIETIN; BACTERIAL-ENDOTOXIN SENSITIZES; OXIDATIVE GLUTAMATE TOXICITY; RECEPTOR SUBUNIT EXPRESSION;
D O I
10.1016/j.ijdevneu.2011.07.008
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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. (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:565 / 582
页数:18
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