Linked Life Data

20035837

Source:http://linkedlifedata.com/resource/pubmed/id/20035837

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2010-2-17
pubmed:abstractText
Damage to oligodendrocyte (OL) progenitor cells (OPCs) and hypomyelination are two hallmark features of periventricular leukomalacia (PVL), the most common form of brain damage in premature infants. Clinical and animal studies have linked the incidence of PVL to maternal infection/inflammation, and activated microglia have been proposed to play a central role. However, the precise mechanism of how activated microglia adversely affects the survival and development of OPCs is still not clear. Here we demonstrate that lipopolysaccharide (LPS)-activated microglia are deleterious to OPCs, that is, impeding OL lineage progression, reducing the production of myelin basic protein (MBP), and mediating OPC death. We further demonstrate that LPS-activated microglia mediate OPC death by two distinct mechanisms in a time-dependent manner. The early phase of cell damage occurs within 24 h after LPS treatment, which is mediated by nitric oxide (NO)-dependent oxidative damage and is prevented by N(G)-nitro-l-arginine methyl ester (l-NAME), a general inhibitor of nitric oxide synthase. The delayed cell death is evident at 48 h after LPS treatment, is mediated by cytokines, and is prevented by blocking the activity of tumor necrosis factor-alpha (TNF-alpha) and pro-nerve growth factor (proNGF), but not by l-NAME. Furthermore, microglia-derived insulin-like growth factor-1 (IGF-1) and ciliary neurotrophic factor (CNTF) were significantly suppressed by LPS, and exogenous IGF-1 and CNTF synergistically protected OLs from death induced by LPS-treated microglia conditioned medium, indicating that a deficiency in trophic support may also be involved in OL death. Our finding that LPS-activated microglia not only induce two waves of cell death but also greatly impair OL development may shed some light on the mechanisms underlying selective white matter damage and hypomyelination in PVL.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1873-7544
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
166
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
464-75
pubmed:meshHeading
pubmed-meshheading:20035837-Analysis of Variance, pubmed-meshheading:20035837-Animals, pubmed-meshheading:20035837-Blotting, Western, pubmed-meshheading:20035837-Cell Death, pubmed-meshheading:20035837-Cell Differentiation, pubmed-meshheading:20035837-Cell Lineage, pubmed-meshheading:20035837-Cell Survival, pubmed-meshheading:20035837-Cells, Cultured, pubmed-meshheading:20035837-Ciliary Neurotrophic Factor, pubmed-meshheading:20035837-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:20035837-Immunohistochemistry, pubmed-meshheading:20035837-Insulin-Like Growth Factor I, pubmed-meshheading:20035837-Lipopolysaccharides, pubmed-meshheading:20035837-Microglia, pubmed-meshheading:20035837-Nerve Fibers, Myelinated, pubmed-meshheading:20035837-Nerve Growth Factor, pubmed-meshheading:20035837-Nitric Oxide, pubmed-meshheading:20035837-Oligodendroglia, pubmed-meshheading:20035837-Oxidative Stress, pubmed-meshheading:20035837-Rats, pubmed-meshheading:20035837-Reactive Oxygen Species, pubmed-meshheading:20035837-Stem Cells, pubmed-meshheading:20035837-Tumor Necrosis Factor-alpha
pubmed:year
2010
pubmed:articleTitle
Lipopolysaccharide-activated microglia induce death of oligodendrocyte progenitor cells and impede their development.
pubmed:affiliation
Department of Pediatrics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural