Abstract |
Diazoxide (DIAZ), an opener of mitochondrial ATP-sensitive K(+) channels (mK( ATP)), protects neurons against hypoxic/ischemic stress in vivo, however, direct evidence showing mitochondrial effects of DIAZ in postischemic neurons is lacking. We investigated if DIAZ affects mitochondrial alterations after global ischemia/reperfusion (I/R) in CA1 pyramidal neurons by using oxalate- pyroantimonate electron cytochemistry. Anesthetized piglets were either non-treated, or treated with DIAZ (3 mg/kg, iv), I/R, DIAZ+I/R, or 5-hydroxy-decanoate (5HD)+DIAZ+I/R (n=6, 6, 11, 5, 7, respectively). Ischemia (10 min) was induced by intracranial pressure (ICP) elevation. After 5-30 min of reperfusion, the brains were fixed for ultrastructural studies. Relative volumes of Ca(2+)-containing deposits and mitochondria in CA1 pyramidal cells were determined by point counting on electron micrographs. I/R resulted in maximal increases in mitochondrial volume (from 7.14+/-0.63% to 9.74+/-0.57%*), and Ca(2+) levels (from 5.86+/-1.11% to 11.39+/-1.35%*; mean+/-S.E.M., *p<0.05) at 10-15-min reperfusion time. In this interval, pretreatment with DIAZ virtually abolished mitochondrial swelling (6.88+/-0.49%) and Ca(2+) accumulation (5.15+/-0.82%) evoked by I/R. The protective effect of DIAZ was reduced by 5HD, an inhibitor of mK( ATP), resulting in a calcium accumulation similar to that after IR (10.44+/-1.98%). Thus, DIAZ might preserve mitochondrial integrity in CA1 pyramidal cells after I/R, at least in part mediated by mK( ATP).
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Authors | Ferenc Domoki, Ferenc Bari, Krisztina Nagy, David W Busija, László Siklós |
Journal | Brain research
(Brain Res)
Vol. 1019
Issue 1-2
Pg. 97-104
(Sep 03 2004)
ISSN: 0006-8993 [Print] Netherlands |
PMID | 15306243
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
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Topics |
- Animals
- Animals, Newborn
- Brain Ischemia
(drug therapy, metabolism, pathology)
- Calcium
(metabolism)
- Diazoxide
(pharmacology, therapeutic use)
- Female
- Male
- Mitochondrial Swelling
(drug effects, physiology)
- Pyramidal Cells
(drug effects, metabolism, pathology)
- Swine
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