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Graded reoxygenation with chemical inhibition of oxidative phosphorylation improves posthypoxic recovery in murine hippocampal slices
Author(s) -
Huber Roman,
Spiegel Tobias,
Büchner Maren,
Riepe Matthias W.
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10868
Subject(s) - oxidative phosphorylation , hippocampal formation , chemistry , phosphorylation , neuroscience , pharmacology , biophysics , psychology , biology , biochemistry
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. © 2003 Wiley‐Liss, Inc.