Diazoxide prevents mitochondrial swelling and Ca2+ accumulation in CA1 pyramidal cells after cerebral ischemia in newborn pigs

F. Domoki, F. Bari, Krisztina Nagy, David W. Busija, L. Siklós

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Diazoxide (DIAZ), an opener of mitochondrial ATP-sensitive K+ channels (mKATP), 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 Ca2+-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 Ca2+ levels (from 5.86±1.11% to 11.39±1.35%*; mean±S.E.M.,*p2+ accumulation (5.15±0.82%) evoked by I/R. The protective effect of DIAZ was reduced by 5HD, an inhibitor of mKATP, 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 mKATP.

Original languageEnglish
Pages (from-to)97-104
Number of pages8
JournalBrain Research
Volume1019
Issue number1-2
DOIs
Publication statusPublished - Sep 3 2004

Fingerprint

Mitochondrial Swelling
Diazoxide
Pyramidal Cells
Brain Ischemia
Swine
Reperfusion
Ischemia
Decanoates
Electrons
Mitochondrial Size
Neurons
Histocytochemistry
Intracranial Hypertension
Oxalates
Mitochondria
Calcium

Keywords

  • Disorders of the nervous system
  • Hippocampus
  • Ischemia
  • Mitochondrial ATP-sensitive potassium channels
  • Neuroprotection
  • Oxalate-pyroantimonate electron cytochemistry
  • Potassium channel opener

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Diazoxide prevents mitochondrial swelling and Ca2+ accumulation in CA1 pyramidal cells after cerebral ischemia in newborn pigs. / Domoki, F.; Bari, F.; Nagy, Krisztina; Busija, David W.; Siklós, L.

In: Brain Research, Vol. 1019, No. 1-2, 03.09.2004, p. 97-104.

Research output: Contribution to journalArticle

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