Linked Life Data

12666262

Source:http://linkedlifedata.com/resource/pubmed/id/12666262

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-4-1
pubmed:abstractText
In cerebral ischemia, the disappointment related to anti-glutamate strategies in clinical trials has led to examine new targets for the treatment of stroke. In vitro studies demonstrated that overactivation of glutamate receptors leads to nitric oxide (NO) production that contributes to the excitotoxic neuronal death. The role of NO was then studied in in vivo models of cerebral ischemia. In the early phase after ischemia, NO is produced by the constitutive endothelial and neuronal isoforms of NO-synthase (NOS 3 and NOS 1) while in the later phase, the inducible NOS (NOS 2) is responsible for the delayed production of NO. NOS 3 appears beneficial via vasodilatation and inhibition of leukocyte adhesion and platelet aggregation. By contrast NOS 1 and NOS 2 were demonstrated deleterious in cerebral ischemia. This was shown by three distinct strategies: selective inhibitors, mutant mice deficient in NOS 1 or NOS 2, and antisenses directed to one of these isoforms. Moreover it is now thought that NO-induced neuronal death is mainly mediated through the formation of peroxynitrite anions resulting from the reaction between NO and superoxyde anion. Peroxynitrites indeed damage lipids, proteins and nucleic acids. DNA strand breaks in turn activate poly(ADP-ribose) polymerase (PARP). Overactivation of this enzyme in pathological conditions such as cerebral ischemia seems deleterious by depleting ATP stores. Thus inhibition of the NO-peroxynitrites-PARP pathway may lead to neuroprotective therapeutics in stroke.
pubmed:language
fre
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0040-5957
pubmed:author
pubmed:issnType
Print
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
548-53
pubmed:dateRevised
2011-10-27
pubmed:meshHeading
pubmed:articleTitle
[NO synthases: new pharmacological targets in cerebrovascular accident?].
pubmed:affiliation
UPRES EA2510, Laboratoire de Pharmacologie, Université René Descartes, Paris, France.
pubmed:publicationType
Journal Article, English Abstract, Review