Document Detail

Role of c-Jun N-terminal kinase in cerebral vasospasm after experimental subarachnoid hemorrhage.
MedLine Citation:
PMID:  15947258     Owner:  NLM     Status:  MEDLINE    
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.
Hiroshi Yatsushige; Mitsuo Yamaguchi; Changman Zhou; John W Calvert; John H Zhang
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Publication Detail:
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:
Title:  Stroke; a journal of cerebral circulation     Volume:  36     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-04     Completed Date:  2005-12-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1538-43     Citation Subset:  IM    
Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
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MeSH Terms
Anthracenes / pharmacology
Blotting, Western
Cytokines / metabolism
Dimethyl Sulfoxide / pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Interleukin-6 / biosynthesis,  cerebrospinal fluid,  metabolism
JNK Mitogen-Activated Protein Kinases / metabolism,  physiology*
Leukocytes / cytology
Signal Transduction
Subarachnoid Hemorrhage / pathology*
Time Factors
Tumor Necrosis Factor-alpha / metabolism
Vasospasm, Intracranial / enzymology*
Grant Support
Reg. No./Substance:
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 Mitogen-Activated Protein Kinases

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