Document Detail


Cilostazol reduces the risk of hemorrhagic infarction after administration of tissue-type plasminogen activator in a murine stroke model.
MedLine Citation:
PMID:  22033992     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: Prior use of antiplatelet agents improves stroke outcome in patients undergoing thrombolytic therapy as shown by reduced arterial reocclusion, although the risk of cerebral hemorrhage can be increased.
METHODS: The effect of cilostazol, an antiplatelet drug that improves endothelial function through upregulation of intracellular cAMP, on cerebral hemorrhage after thrombolytic therapy was investigated using a highly reproducible transient ischemia model.
RESULTS: Treatment with cilostazol for 7 days before ischemia significantly suppressed the risk and severity of cerebral hemorrhage after injection of tissue-type plasminogen activator, although treatment with aspirin had no such protective effect compared with nontreated mice. Immunohistological analysis revealed that treatment with cilostazol suppressed disruption of the microvasculature in the ischemic area associated with reduced matrix metalloproteinase-9 activity.
CONCLUSIONS: Our results suggest that patients treated with cilostazol before onset of stroke could have a lower risk of cerebral hemorrhage after thrombolytic therapy and might also have a longer therapeutic time window for thrombolysis. Furthermore, the risk of cerebral hemorrhage can be significantly altered by prestroke therapies, and analysis of the effects of multiple drugs on tissue-type plasminogen activator-induced cerebral hemorrhage in animal models is essential for the extending safe and effective thrombolytic therapy to a wider group of patients.
Authors:
Yukiko Kasahara; Takayuki Nakagomi; Tomohiro Matsuyama; David Stern; Akihiko Taguchi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-27
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  43     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-01-24     Completed Date:  2012-08-15     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  499-506     Citation Subset:  IM    
Affiliation:
Department of Cerebrovascular Disease, National Cerebral and Cardiovascular Center, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspirin / therapeutic use
Brain / pathology
Cerebral Hemorrhage / chemically induced,  pathology,  prevention & control*
Cerebral Infarction / chemically induced,  pathology,  prevention & control*
Immunohistochemistry
Ischemic Attack, Transient / prevention & control
Male
Matrix Metalloproteinase 9 / biosynthesis
Mice
Mice, Inbred ICR
Neuroprotective Agents / therapeutic use*
Platelet Aggregation Inhibitors / therapeutic use*
Reperfusion Injury / prevention & control
Stroke / chemically induced,  prevention & control*
Tetrazoles / therapeutic use*
Tissue Plasminogen Activator*
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Platelet Aggregation Inhibitors; 0/Tetrazoles; 50-78-2/Aspirin; EC 3.4.21.68/Tissue Plasminogen Activator; EC 3.4.24.35/Matrix Metalloproteinase 9; N7Z035406B/cilostazol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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