| Fingolimod reduces hemorrhagic transformation associated with delayed tissue plasminogen activator treatment in a mouse thromboembolic model. | |
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MedLine Citation:
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PMID: 23287783 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Francisco Campos; Tao Qin; José Castillo; Ji Hae Seo; Ken Arai; Eng H Lo; Christian Waeber |
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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 Date: 2013-01-03 |
Journal Detail:
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Title: Stroke; a journal of cerebral circulation Volume: 44 ISSN: 1524-4628 ISO Abbreviation: Stroke Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-21 Completed Date: 2013-03-11 Revised Date: 2013-04-16 |
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: 505-11 Citation Subset: IM |
Affiliation:
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Stroke Research Laboratory, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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:
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0/Neuroprotective Agents; 0/Propylene Glycols; 123-78-4/Sphingosine; 3QN8BYN5QF/fingolimod; EC 3.4.21.68/Tissue Plasminogen Activator |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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