Linked Life Data

7798922

Source:http://linkedlifedata.com/resource/pubmed/id/7798922

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1995-1-24
pubmed:abstractText
The role of inflammatory cytokines in the pathogenesis of neurological disorders is not entirely clear. The neurotoxic effects of cytokines, and perhaps indirectly bacterial endotoxins, could be mediated by the stimulation of immunocompetent cells in the brain to produce toxic concentrations of nitric oxide (NO) and reactive nitrogen oxides. NO is a short-lived, diffusible molecule that has a variety of biological activities including vasorelaxation, neurotransmission, and cytotoxicity. Both constitutive and inducible NO synthase has been described in astrocytes in vitro. Here we demonstrate that newborn mouse cortical astrocytes, when coincubated with neonatal mouse cerebellar granule cells or hippocampal neurons, induced neurotoxicity upon stimulation with endotoxin (lipopolysaccharide) (ED50 30 ng/ml). Astrocytes were unresponsive to the cytokines tumor necrosis factor-alpha or interleukin-1 beta individually, but exhibited a marked synergistic stimulation in their combined presence. Moreover, meningeal fibroblasts treated with tumor necrosis factor-alpha, but not interleukin-1 beta or lipopolysaccharide, elaborated neurotoxicity for cocultured granule cells (ED50 30 U/ml). In cocultures of immunostimulated astrocytes or meningeal fibroblasts, neurotoxicity was blocked by the NO synthase inhibitors N omega-nitro-L-arginine and N omega-nitro-D-arginine methyl ester, and by oxyhemoglobin, which inactivates NO. Astroglial-induced neurotoxicity was not affected by N-methyl-D-aspartate receptor antagonists. Superoxide dismutase, which degrades superoxide anion, attenuated astrocyte- and fibroblast-mediated neurotoxicity, indicating that endogenous superoxide anion may react with NO to form toxic peroxynitrite and its breakdown products. These findings suggest a potentially important role for glial- and meningeal fibroblast-induced NO synthase in the pathophysiology of CNS disease states of immune or inflammatory origin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
266-76
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Inflammatory mediator stimulation of astrocytes and meningeal fibroblasts induces neuronal degeneration via the nitridergic pathway.
pubmed:affiliation
Researchlife S.c.p.A., Centro di Ricerca Biomedica, Ospedale Civile, Castelfranco Veneto, Italy.
pubmed:publicationType
Journal Article