| Uncoupling of endothelial nitric oxide synthase after experimental subarachnoid hemorrhage. | |
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MedLine Citation:
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PMID: 20517322 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We studied whether endothelial nitric oxide synthase (eNOS) is upregulated and uncoupled in large cerebral arteries after subarachnoid hemorrhage (SAH) and also whether this causes cerebral vasospasm in a mouse model of anterior circulation SAH. Control animals underwent injection of saline instead of blood (n=16 SAH and n=16 controls). There was significant vasospasm of the middle cerebral artery 2 days after SAH (lumen radius/wall thickness ratio 4.3 ± 1.3 for SAH, 23.2 ± 2.1 for saline, P<0.001). Subarachnoid hemorrhage was associated with terminal deoxynucleotidyl transferase dUTP nick-end labeling, cleaved caspase-3, and Fluoro-Jade-positive neurons in the cortex and with CA1 and dentate regions in the hippocampus. There were multiple fibrinogen-positive microthromboemboli in the cortex and hippocampus after SAH. Transgenic mice expressing lacZ under control of the eNOS promoter had increased X-gal staining in large arteries after SAH, and this was confirmed by the increased eNOS protein on western blotting. Evidence that eNOS was uncoupled was found in that nitric oxide availability was decreased, and superoxide and peroxynitrite concentrations were increased in the brains of mice with SAH. This study suggests that artery constriction by SAH upregulates eNOS but that it is uncoupled and produces peroxynitrite that may generate microemboli that travel distally and contribute to brain injury. |
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Authors:
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Mohammed Sabri; Jinglu Ai; Britta Knight; Asma Tariq; Hyojin Jeon; Xueyuan Shang; Philip Anthony Marsden; Robert Loch Macdonald |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-06-02 |
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: 31 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-04 Completed Date: 2011-02-03 Revised Date: 2012-01-02 |
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: 190-9 Citation Subset: IM |
Affiliation:
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Division of Neurosurgery, St Michael's Hospital, Keenan Research Centre in Li Ka Shing Knowledge Institute of St Michael's Hospital and Department of Surgery, University of Toronto, Toronto, Ontario, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arterioles / enzymology, pathology Blotting, Western Caspase 3 / metabolism Cerebral Arteries / enzymology, pathology Fibrinogen / metabolism Immunohistochemistry In Situ Nick-End Labeling Intracranial Thrombosis / enzymology, pathology Lac Operon / genetics Mice Mice, Transgenic Nitric Oxide / metabolism Nitric Oxide Synthase Type II / genetics, metabolism Nitric Oxide Synthase Type III / genetics, metabolism* Peroxynitrous Acid / metabolism Subarachnoid Hemorrhage / enzymology*, genetics Superoxides / metabolism Tyrosine / analogs & derivatives, metabolism Vasospasm, Intracranial / enzymology |
| Chemical | |
Reg. No./Substance:
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10102-43-9/Nitric Oxide; 11062-77-4/Superoxides; 14691-52-2/Peroxynitrous Acid; 3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; 9001-32-5/Fibrinogen; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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