Document Detail


Increased brain injury and vascular leakage after pretreatment with p38-inhibitor SB203580 in transient ischemia.
MedLine Citation:
PMID:  14616304     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: Focal cerebral ischemia activates intracellular signaling pathways including the mitogen-activated protein kinase p38, which may be involved in the process of ischemic brain injury. In this study, the effect of pretreatment with the p38-inhibitor SB203580 on infarct size and blood-brain barrier (BBB) breakdown was investigated with magnetic resonance imaging (MRI). MATERIALS AND METHODS: Rats were given SB203580 (n = 6) or vehicle (n = 6) in the right lateral ventricle prior to transient (90 min) middle cerebral artery occlusion (MCAO) on the left side. The rats were examined with serial MRI during MCAO, at reperfusion and after 1 and 4 days. RESULTS: The mean infarct size on T2-weighted images after 1 day was significantly higher in the SB203580-treated group than in controls (300 +/- 95 mm3 vs 126 +/- 75 mm3; P < 0.01). Vascular gadolinium leakage, indicating BBB breakdown, was significantly larger in the SB203580-treated group than in controls after 1 day (median leakage score 18.5; range 15-21 vs 6.5; 4-17; P < 0.05) and 4 days (11; 6-15 vs 3.5; 1-9; P < 0.05), although no significant difference was seen initially. CONCLUSION: Pretreatment with SB203580 may aggravate ischemic brain injury and cerebral vascular leakage in the present model of transient ischemia.
Authors:
F Lennmyr; A Ericsson; P Gerwins; H Ahlström; A Terént
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Acta neurologica Scandinavica     Volume:  108     ISSN:  0001-6314     ISO Abbreviation:  Acta Neurol. Scand.     Publication Date:  2003 Nov 
Date Detail:
Created Date:  2003-11-17     Completed Date:  2004-01-30     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0370336     Medline TA:  Acta Neurol Scand     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  339-45     Citation Subset:  IM    
Affiliation:
Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University Hospital, Uppsala, Sweden. fredrik.lennmyr@surgsci.uu.se
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood-Brain Barrier*
Brain Edema / etiology,  pathology*
Capillary Permeability
Cerebrovascular Circulation
Imidazoles / pharmacology*
Infarction, Middle Cerebral Artery / complications,  pathology
Ischemic Attack, Transient / etiology,  pathology*
Magnetic Resonance Imaging
Male
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Pyridines / pharmacology*
Rats
Rats, Sprague-Dawley
Reperfusion
Treatment Outcome
p38 Mitogen-Activated Protein Kinases
Chemical
Reg. No./Substance:
0/Imidazoles; 0/Pyridines; 0/SB 203580; EC 2.7.11.24/Mitogen-Activated Protein Kinases; EC 2.7.11.24/p38 Mitogen-Activated Protein Kinases

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