| Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery. | |
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MedLine Citation:
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PMID: 19718040 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Here we show that ischemia induces sustained contraction of pericytes on microvessels in the intact mouse brain. Pericytes remain contracted despite successful reopening of the middle cerebral artery after 2 h of ischemia. Pericyte contraction causes capillary constriction and obstructs erythrocyte flow. Suppression of oxidative-nitrative stress relieves pericyte contraction, reduces erythrocyte entrapment and restores microvascular patency; hence, tissue survival improves. In contrast, peroxynitrite application causes pericyte contraction. We also show that the microvessel wall is the major source of oxygen and nitrogen radicals causing ischemia and reperfusion-induced microvascular dysfunction. These findings point to a major but previously not recognized pathophysiological mechanism; ischemia and reperfusion-induced injury to pericytes may impair microcirculatory reflow and negatively affect survival by limiting substrate and drug delivery to tissue already under metabolic stress, despite recanalization of an occluded artery. Agents that can restore pericyte dysfunction and microvascular patency may increase the success of thrombolytic and neuroprotective treatments. |
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Authors:
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Muge Yemisci; Yasemin Gursoy-Ozdemir; Atay Vural; Alp Can; Kamil Topalkara; Turgay Dalkara |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-30 |
Journal Detail:
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Title: Nature medicine Volume: 15 ISSN: 1546-170X ISO Abbreviation: Nat. Med. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-07 Completed Date: 2009-10-02 Revised Date: 2010-09-15 |
Medline Journal Info:
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Nlm Unique ID: 9502015 Medline TA: Nat Med Country: United States |
Other Details:
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Languages: eng Pagination: 1031-7 Citation Subset: IM |
Affiliation:
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Department of Neurology, Faculty of Medicine and Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Brain Ischemia / pathology*, physiopathology* Capillaries / physiopathology Cell Size Enzyme Inhibitors / pharmacology Mice Mice, Knockout Microscopy, Fluorescence Microscopy, Interference Middle Cerebral Artery / pathology, physiopathology* Nitric Oxide Synthase Type I / deficiency, genetics Nitric Oxide Synthase Type III / antagonists & inhibitors Ornithine / analogs & derivatives, pharmacology Oxidative Stress Pericytes / pathology*, physiology* Reactive Nitrogen Species / metabolism Reactive Oxygen Species / metabolism Reperfusion Injury / pathology, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Reactive Nitrogen Species; 0/Reactive Oxygen Species; 36889-13-1/N(G)-iminoethylornithine; 7006-33-9/Ornithine; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos1 protein, mouse; EC 1.14.13.39/Nos3 protein, mouse |
| Comments/Corrections | |
Comment In:
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Nat Med. 2010 Sep;16(9):959; author reply 960
[PMID:
20823870
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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