MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat

Katsuyoshi Shimizu, Zsombor Lacza, Nishadi Rajapakse, Takashi Horiguchi, James Snipes, David W. Busija

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

We investigated effects of diazoxide, a selective opener of mitochondrial ATP-sensitive K+ (mitoKATP) channels, against brain damage after middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (0.4 or 2 mM in 30 μl saline) or saline (sham) was infused into the right lateral ventricle 15 min before MCAO. Neurological score was improved 24 h later in the animals treated with 2 mM diazoxide (13.8 ± 0.7, n = 13) compared with sham treatment (9.5 ± 0.2, n = 6, P < 0.01). The total percent infarct volume (MCAO vs. contralateral side) of sham treatment animals was 43.6 ± 3.6% (n = 12). Treatment with 2 mM diazoxide reduced the infarct volume to 20.9 ± 4.8% (n = 13, P < 0.05). Effects of diazoxide were prominent in the cerebral cortex. The protective effect of diazoxide was completely prevented by the pretreatment with 5-hydroxydecanoate (100 mM in 10 μl saline), a selective blocker of mitoKATP channels (n = 6). These results indicate that selective opening of the mitoKATP channel has neuroprotective effects against ischemia-reperfusion injury in the rat brain.

Original languageEnglish
Pages (from-to)H1005-H1011
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number3 52-3
DOIs
Publication statusPublished - 2002

Keywords

  • Cerebral circulation
  • Ischemia
  • Mitochondrial adenosine 5′-triphosphate-sensitive potassium channels
  • Stroke

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Fingerprint Dive into the research topics of 'MitoK<sub>ATP</sub> opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat'. Together they form a unique fingerprint.

  • Cite this