Document Detail


Graded reoxygenation with chemical inhibition of oxidative phosphorylation improves posthypoxic recovery in murine hippocampal slices.
MedLine Citation:
PMID:  14743458     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Rapid and complete tissue reoxygenation is a prime goal of present stroke therapy. However, reoxygenation may trigger detrimental cascades that partially antagonize beneficial effects. It was our goal to investigate selective grading of reoxygenation with targeting of single mitochondrial complexes in murine hippocampal slices. Population spike amplitude (PSAP) and NADH were measured during hypoxic hypoxia (15 min) and recovery (45 min). With onset of reoxygenation, slices were treated for different times with amobarbital (1 mM), malonate (2 mM), or cyanide (1 mM), inhibitors of mitochondrial complex I, II, or IV, respectively. Other slices were treated with nicotinamide (1 mM). Posthypoxic recovery of PSAP increased from 32% +/- 43% of onset in control slices to 52% +/- 59% (P <.05) upon treatment with amobarbital for 1 min and to 62% +/- 37% (P <.05) upon treatment with malonate. With nicotinamide, posthypoxic recovery improved to 73% +/- 25% (P <.05). Oxidation of NADH was prolonged upon treatment with amobarbital, whereas no change in NADH oxidation was observed with malonate and nicotinamide. Thus, grading of reoxygenation with selective targeting of mitochondrial complex I or II but not of complex IV improves outcome upon reoxygenation in murine hippocampal slices.
Authors:
Roman Huber; Tobias Spiegel; Maren Büchner; Matthias W Riepe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  75     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2004 Feb 
Date Detail:
Created Date:  2004-01-26     Completed Date:  2004-03-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  441-9     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Affiliation:
Department of Neurology, University of Ulm, Ulm, Germany.
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects*,  physiology
Amobarbital / pharmacology
Animals
Anoxia / metabolism*
Cyanides / pharmacology
Electron Transport Complex I / antagonists & inhibitors
Electron Transport Complex II / antagonists & inhibitors
Electron Transport Complex IV / antagonists & inhibitors
Hippocampus / drug effects,  metabolism*
Male
Malonates / pharmacology
Mice
NAD / metabolism
Niacinamide / pharmacology
Organ Culture Techniques
Oxidative Phosphorylation / drug effects*
Reperfusion*
Chemical
Reg. No./Substance:
0/Cyanides; 0/Malonates; 141-82-2/malonic acid; 53-84-9/NAD; 57-43-2/Amobarbital; 98-92-0/Niacinamide; EC 1.3.5.1/Electron Transport Complex II; EC 1.6.5.3/Electron Transport Complex I; EC 1.9.3.1/Electron Transport Complex IV

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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