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

102 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
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume283
Issue number3 52-3
Publication statusPublished - 2002
Externally publishedYes

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Diazoxide
Middle Cerebral Artery Infarction
Placebos
Lateral Ventricles
Brain
Neuroprotective Agents
Reperfusion Injury
Cerebral Cortex
Heart Ventricles
Wistar Rats
Adenosine Triphosphate
mitochondrial K(ATP) channel

Keywords

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

ASJC Scopus subject areas

  • Physiology

Cite this

MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat. / Shimizu, Katsuyoshi; Lacza, Zsombor; Rajapakse, Nishadi; Horiguchi, Takashi; Snipes, James; Busija, David W.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 283, No. 3 52-3, 2002.

Research output: Contribution to journalArticle

Shimizu, Katsuyoshi ; Lacza, Zsombor ; Rajapakse, Nishadi ; Horiguchi, Takashi ; Snipes, James ; Busija, David W. / MitoKATP opener, diazoxide, reduces neuronal damage after middle cerebral artery occlusion in the rat. In: American Journal of Physiology - Heart and Circulatory Physiology. 2002 ; Vol. 283, No. 3 52-3.
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