Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2005-12-7
pubmed:abstractText
Considering its brain-specific expression, neuroserpin (NS), a potent inhibitor of tissue-type plasminogen activator (tPA), might be a good therapeutic target to limit the pro-excitotoxic effects of tPA within the cerebral parenchyma, without affecting the benefit from thrombolysis in stroke patients. Here, we aimed at determining the mechanisms of action responsible for the previously reported neuroprotective activity of NS in rodent experimental cerebral ischemia. First, we show in vivo that exogenous NS protects the cortex and the striatum against NMDA-induced injury. Then, the cellular mechanisms of this neuroprotection were investigated in primary cultures of cortical neurons. We show that NS fails to prevent serum deprivation-induced apoptotic neuronal death, while it selectively prevents NMDA- but not AMPA-induced excitotoxicity. This beneficial effect is associated to a decrease in NMDA receptor-mediated intracellular calcium influx. Altogether, these data suggest that an overexpression of neuroserpin in the brain parenchyma might limit the deleterious effect of tPA on NMDA receptor-mediated neuronal death, which occurs following experimental ischemia.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1044-7431
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
552-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16209928-Animals, pubmed-meshheading:16209928-Apoptosis, pubmed-meshheading:16209928-Brain, pubmed-meshheading:16209928-Brain Ischemia, pubmed-meshheading:16209928-Calcium Signaling, pubmed-meshheading:16209928-Cells, Cultured, pubmed-meshheading:16209928-Cerebral Cortex, pubmed-meshheading:16209928-Corpus Striatum, pubmed-meshheading:16209928-Disease Models, Animal, pubmed-meshheading:16209928-Male, pubmed-meshheading:16209928-Mice, pubmed-meshheading:16209928-N-Methylaspartate, pubmed-meshheading:16209928-Neurons, pubmed-meshheading:16209928-Neuropeptides, pubmed-meshheading:16209928-Neuroprotective Agents, pubmed-meshheading:16209928-Neurotoxins, pubmed-meshheading:16209928-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:16209928-Serpins, pubmed-meshheading:16209928-Stroke
pubmed:year
2005
pubmed:articleTitle
The brain-specific tissue-type plasminogen activator inhibitor, neuroserpin, protects neurons against excitotoxicity both in vitro and in vivo.
pubmed:affiliation
INSERM-Avenir, tPA in the working brain, GIP CYCERON, Université de Caen, GIP Cyceron-Bd Henri Becquerel, 14074 Caen Cedex, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't