| Role of c-Jun N-terminal kinase in cerebral vasospasm after experimental subarachnoid hemorrhage. | |
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MedLine Citation:
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PMID: 15947258 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND AND PURPOSE: Inflammation could play a role in cerebral vasospasm after subarachnoid hemorrhage (SAH). SP600125 a c-Jun N-terminal kinase (JNK) inhibitor reduces inflammation. The present study examined if SP600125 could reduce cerebral vasospasm. METHODS: Twenty-seven dogs were assigned to 5 groups: control, SAH, SAH plus dimethyl sulfoxide (DMSO), SAH plus SP600125 (10 micromol/L), and SAH plus SP600125 (30 micromol/L). SAH was induced by the injection of autologous blood into the cisterna magna on day 0 and day 2. Angiograms were evaluated on day 0 and day 7. The behavior of the dogs was evaluated daily. The activation of the JNK pathway, the infiltration of leukocytes, and the production of cytokines were also evaluated. RESULTS: Severe vasospasm was observed in the basilar artery of SAH and DMSO dogs. The JNK signaling pathway was activated in the basilar artery after SAH and SP600125 reduced angiographic and morphological vasospasm and improved behavior scores with a concomitant reduction of infiltrated leukocytes and IL-6 production. CONCLUSIONS: These results demonstrate that SP600125 attenuated cerebral vasospasm through a suppressed inflammatory response, which may provide a novel therapeutic target for cerebral vasospasm. |
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Authors:
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Hiroshi Yatsushige; Mitsuo Yamaguchi; Changman Zhou; John W Calvert; John H Zhang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2005-06-09 |
Journal Detail:
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Title: Stroke; a journal of cerebral circulation Volume: 36 ISSN: 1524-4628 ISO Abbreviation: Stroke Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-07-04 Completed Date: 2005-12-02 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 0235266 Medline TA: Stroke Country: United States |
Other Details:
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Languages: eng Pagination: 1538-43 Citation Subset: IM |
Affiliation:
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Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiography Animals Anthracenes / pharmacology Blotting, Western Cytokines / metabolism Dimethyl Sulfoxide / pharmacology Dogs Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Hemorrhage Immunohistochemistry Inflammation Interleukin-6 / biosynthesis, cerebrospinal fluid, metabolism JNK Mitogen-Activated Protein Kinases / metabolism, physiology* Leukocytes / cytology Phosphorylation Signal Transduction Subarachnoid Hemorrhage / pathology* Time Factors Tumor Necrosis Factor-alpha / metabolism Vasospasm, Intracranial / enzymology* |
| Grant Support | |
ID/Acronym/Agency:
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HD43120/HD/NICHD NIH HHS; NS43338/NS/NINDS NIH HHS; NS45694/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Anthracenes; 0/Cytokines; 0/Enzyme Inhibitors; 0/Interleukin-6; 0/Tumor Necrosis Factor-alpha; 0/anthra(1,9-cd)pyrazol-6(2H)-one; 67-68-5/Dimethyl Sulfoxide; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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