Source:http://linkedlifedata.com/resource/pubmed/id/18835333
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2008-11-18
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pubmed:abstractText |
Cerebral ischemia induces Ca(2+) influx into neuronal cells, and activates several proteases including calpains. Since calpains play important roles in neuronal cell death, calpain inhibitors may have potential as drugs for cerebral infarction. ((1S)-1((((1S)-1-Benzyl-3- cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester (SNJ-1945) is a novel calpain inhibitor that has good membrane permeability and water solubility. We evaluated the effect of SNJ-1945 on the focal brain ischemia induced by middle cerebral artery occlusion (MCAO) in mice. Brain damage was evaluated by assessing neurological deficits at 24 h or 72 h after MCAO and also by examining 2,3,5-triphenyltetrazolium chloride (TTC) staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining of brain sections. When injected at 1 h after MCAO, SNJ-1945 at 30 and 100 mg/kg, i.p. decreased the infarction volume and improved the neurological deficits each assessed at 24 h. SNJ-1945 at 100 mg/kg, i.p. also showed neuroprotective effects at 72 h and reduced the number of TUNEL-positive cells at 24 h. SNJ-1945 was able to prevent neuronal cell death even when it was injected at up to 6 h, but not at 8 h, after MCAO. In addition, SNJ-1945 decreased cleaved alpha-spectrin at 6 h and 12 h, and active caspase-3 at 12 h and 24 h in ischemic brain hemisphere. These findings indicate that SNJ-1945 inhibits the activation of calpain, and offers neuroprotection against the effects of acute cerebral ischemia in mice even when given up to 6 h after MCAO. SNJ-1945 may therefore be a potential drug for stroke.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/((1S)-1-((((1S)-1-benzyl-3-cycloprop...,
http://linkedlifedata.com/resource/pubmed/chemical/Carbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Docosahexaenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Spectrin,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrazolium Salts,
http://linkedlifedata.com/resource/pubmed/chemical/triphenyltetrazolium
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0306-4522
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
19
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pubmed:volume |
157
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
309-18
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pubmed:meshHeading |
pubmed-meshheading:18835333-Analysis of Variance,
pubmed-meshheading:18835333-Animals,
pubmed-meshheading:18835333-Brain Ischemia,
pubmed-meshheading:18835333-Carbamates,
pubmed-meshheading:18835333-Caspase 3,
pubmed-meshheading:18835333-Cell Death,
pubmed-meshheading:18835333-Cerebral Infarction,
pubmed-meshheading:18835333-Disease Models, Animal,
pubmed-meshheading:18835333-Docosahexaenoic Acids,
pubmed-meshheading:18835333-Dose-Response Relationship, Drug,
pubmed-meshheading:18835333-In Situ Nick-End Labeling,
pubmed-meshheading:18835333-Male,
pubmed-meshheading:18835333-Mice,
pubmed-meshheading:18835333-Neurologic Examination,
pubmed-meshheading:18835333-Spectrin,
pubmed-meshheading:18835333-Tetrazolium Salts,
pubmed-meshheading:18835333-Time Factors
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pubmed:year |
2008
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pubmed:articleTitle |
A novel calpain inhibitor, ((1S)-1((((1S)-1-benzyl-3-cyclopropylamino-2,3-di-oxopropyl)amino)carbonyl)-3-methylbutyl) carbamic acid 5-methoxy-3-oxapentyl ester, protects neuronal cells from cerebral ischemia-induced damage in mice.
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pubmed:affiliation |
Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-5858, Japan.
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pubmed:publicationType |
Journal Article
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