Document Detail


Pericyte contraction induced by oxidative-nitrative stress impairs capillary reflow despite successful opening of an occluded cerebral artery.
MedLine Citation:
PMID:  19718040     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Muge Yemisci; Yasemin Gursoy-Ozdemir; Atay Vural; Alp Can; Kamil Topalkara; Turgay Dalkara
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-30
Journal Detail:
Title:  Nature medicine     Volume:  15     ISSN:  1546-170X     ISO Abbreviation:  Nat. Med.     Publication Date:  2009 Sep 
Date Detail:
Created Date:  2009-09-07     Completed Date:  2009-10-02     Revised Date:  2010-09-15    
Medline Journal Info:
Nlm Unique ID:  9502015     Medline TA:  Nat Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1031-7     Citation Subset:  IM    
Affiliation:
Department of Neurology, Faculty of Medicine and Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
Nat Med. 2010 Sep;16(9):959; author reply 960   [PMID:  20823870 ]

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