| Deficiency of PAR4 attenuates cerebral ischemia/reperfusion injury in mice. | |
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MedLine Citation:
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PMID: 20087365 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Stroke is the third leading cause of death in the USA. Antithrombotic therapy targeting platelet activation is one of the treatments for ischemic stroke. Here we investigate the role of one of the thrombin receptors, protease-activated receptor 4 (PAR4), in a mouse transient middle cerebral artery occlusion (MCAO) model. After a 60 min MCAO and 23 h reperfusion, leukocyte and platelet rolling and adhesion on cerebral venules, blood-brain barrier (BBB) permeability, and cerebral edema were compared in PAR4-deficient mice and wild-type mice. Cerebral infarction volume and neuronal death were also measured. PAR4-/- mice had more than an 80% reduction of infarct volume and significantly improved neurologic and motor function compared with wild-type mice after MCAO. Furthermore, deficiency of PAR4 significantly inhibits the rolling and adhesion of both platelets and leukocytes after MCAO. BBB disruption and cerebral edema were also attenuated in PAR4-/- mice compared with wild-type animals. The results of this investigation indicate that deficiency of PAR4 protects mice from cerebral ischemia/reperfusion (I/R) injury, partially through inhibition of platelet activation and attenuation of microvascular inflammation. |
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Authors:
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Yingying Mao; Ming Zhang; Ronald F Tuma; Satya P Kunapuli |
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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: 2010-01-20 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 30 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-03 Completed Date: 2010-05-27 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 1044-52 Citation Subset: IM |
Affiliation:
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Department of Physiology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood Platelets / metabolism Blood-Brain Barrier / metabolism Brain Edema / pathology, physiopathology Brain Ischemia / metabolism*, pathology, physiopathology Cerebrovascular Circulation Endothelial Cells / metabolism Hippocampus / cytology, pathology Humans Infarction, Middle Cerebral Artery Leukocyte Rolling Mice Mice, Knockout Neuropsychological Tests Platelet Activation Receptors, Proteinase-Activated / genetics, metabolism* Reperfusion Injury / metabolism*, pathology, physiopathology |
| Grant Support | |
ID/Acronym/Agency:
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DA 03672/DA/NIDA NIH HHS; DA 05488/DA/NIDA NIH HHS; DA P30 13429/DA/NIDA NIH HHS; HL60683/HL/NHLBI NIH HHS; HL80444/HL/NHLBI NIH HHS; HL81322/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Receptors, Proteinase-Activated; 0/protease-activated receptor 4, mouse |
| Comments/Corrections | |
Erratum In:
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J Cereb Blood Flow Metab. 2010 Jun;30(6):1261 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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