Document Detail


Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model.
MedLine Citation:
PMID:  23287783     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: The sphingosine 1-phosphate receptor agonist fingolimod reduces infarct size in rodent models of stroke and enhances blood-brain barrier integrity. Based on these observations, we hypothesized that combination of fingolimod with tissue plasminogen activator (tPA) would reduce the risk of hemorrhagic transformation associated with delayed administration of tPA.
METHODS: We evaluated the effects of fingolimod in a mouse model of thromboembolic stroke, in which both the beneficial effect of reperfusion associated with early tPA treatment and hemorrhagic transformation associated with delayed administration mimic clinical observations in humans.
RESULTS: Our results demonstrate that fingolimod treatment attenuates the neurological deficit and reduces infarct volume after in situ thromboembolic occlusion of the middle cerebral artery. Combination of fingolimod and tPA improves the neurological outcome of the thrombolytic therapy and reduces the risk of hemorrhagic transformation associated with delayed administration of tPA.
CONCLUSIONS: This study confirms the protective efficacy of fingolimod as a treatment against ischemic stroke in another rodent model of stroke (thromboembolic occlusion), and suggests that fingolimod could potentially be used in combination with tPA to reduce the risk of brain hemorrhage.
Authors:
Francisco Campos; Tao Qin; José Castillo; Ji Hae Seo; Ken Arai; Eng H Lo; Christian Waeber
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-03
Journal Detail:
Title:  Stroke; a journal of cerebral circulation     Volume:  44     ISSN:  1524-4628     ISO Abbreviation:  Stroke     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-21     Completed Date:  2013-03-11     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0235266     Medline TA:  Stroke     Country:  United States    
Other Details:
Languages:  eng     Pagination:  505-11     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebral Hemorrhage / pathology,  prevention & control*
Disease Models, Animal*
Male
Mice
Mice, Inbred C57BL
Neuroprotective Agents / administration & dosage
Propylene Glycols / administration & dosage*
Sphingosine / administration & dosage,  analogs & derivatives*
Thromboembolism / drug therapy*,  pathology
Time Factors
Tissue Plasminogen Activator / administration & dosage*
Treatment Outcome
Grant Support
ID/Acronym/Agency:
NS049263/NS/NINDS NIH HHS; NS055104/NS/NINDS NIH HHS; P01 NS055104/NS/NINDS NIH HHS; P30 NS045776/NS/NINDS NIH HHS; P30NS045776/NS/NINDS NIH HHS; R01 NS049263/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Neuroprotective Agents; 0/Propylene Glycols; 3QN8BYN5QF/fingolimod; EC 3.4.21.68/Tissue Plasminogen Activator; NGZ37HRE42/Sphingosine
Comments/Corrections

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


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