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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-3-10
pubmed:abstractText
Inflammatory responses have been known to contribute to the development of neuronal damage after brain ischemia in experimental animals. Also, neutrophil elastase activity in the plasma has been elevated in the patients with acute cerebral infarction. In order to clarify whether neutrophil elastase distributes into the brain parenchyma and exacerbates neuronal damage following ischemia, we examined the effects of specific neutrophil elastase inhibitor, ONO-5046, on hippocampal CA1 neuronal death in relation to neutrophil elastase activity in the plasma and its distribution in the brain and to caspase-3/7 activity. ONO-5046 (5 and 10 mg/kg) or saline (control group) was administrated after 8 min of forebrain ischemia in rats. Ratio of surviving neurons (median, [range]) in hippocampal CA1 seven days after ischemia was significantly higher in the ONO-5046 5 mg/kg (31% [12-57%]), and 10 mg/kg groups (69% [39-76%]) than in the control group (3.2% [0-10%]). Plasma neutrophil elastase activity in the ONO-5046 10 mg/kg group was significantly lower than in the control group (14 [11-25] vs. 41 [35-68] nmol/ml). Neutrophil elastase distributed in the extracellular space in the hippocampal CA1 neuronal layer in the control group, while, in the ONO-5046 10 mg/kg group, trace of neutrophil elastase was detected only in the endothelium. Caspase-3/7 activity was elevated after ischemia over 8 h in the control group, while, in the ONO-5046 10 mg/kg group, no elevation was observed. The results suggest that neutrophil elastase may contribute to neuronal death in hippocampal CA1 following forebrain ischemia and that neutrophil elastase inhibitor attenuates neuronal death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1872-6240
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
1259
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
98-106
pubmed:meshHeading
pubmed-meshheading:19168036-Animals, pubmed-meshheading:19168036-Brain, pubmed-meshheading:19168036-Brain Ischemia, pubmed-meshheading:19168036-Caspase 3, pubmed-meshheading:19168036-Caspase 7, pubmed-meshheading:19168036-Cell Survival, pubmed-meshheading:19168036-Endothelium, pubmed-meshheading:19168036-Extracellular Space, pubmed-meshheading:19168036-Glycine, pubmed-meshheading:19168036-Leukocyte Elastase, pubmed-meshheading:19168036-Male, pubmed-meshheading:19168036-Neurons, pubmed-meshheading:19168036-Neuroprotective Agents, pubmed-meshheading:19168036-Proteinase Inhibitory Proteins, Secretory, pubmed-meshheading:19168036-Rats, pubmed-meshheading:19168036-Rats, Wistar, pubmed-meshheading:19168036-Reperfusion, pubmed-meshheading:19168036-Sulfonamides, pubmed-meshheading:19168036-Time Factors
pubmed:year
2009
pubmed:articleTitle
Neutrophil elastase inhibitor attenuates hippocampal neuronal damage after transient forebrain ischemia in rats.
pubmed:affiliation
Department of Anesthesiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi, 755-8505 Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't