Premium
Diazoxide induces delayed preconditioning against transient focal cerebral ischemia in Rats
Author(s) -
Mayanagi Keita,
Lenzser Gabor,
Gaspar Tamas,
Busija David W.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a779-a
Subject(s) - diazoxide , ischemia , medicine , in vivo , anesthesia , potassium channel , pharmacology , endocrinology , biology , insulin , microbiology and biotechnology
Diazoxide is the prototypical opener of mitochondrial ATP‐sensitive potassium channels (mitoK ATP ) and protects neurons in vivo and in vitro against chemical and anoxic stresses. While we have previously shown that diazoxide administration induces delayed protection of the blood‐brain barrier against ischemic damage in rats ( Brain Res. 2005; 1051 :–80), we did not examine whether diazoxide limits infarct volume in stroke. The purpose of this study was to determine whether diazoxide promotes delayed preconditioning against experimental strokes. We tested the delayed effect of Diazoxide on 90 min middle cerebral artery occlusion (MCAO) in male Wistar rats. Diazoxide (10mg/kg) was injected 24 hours before MCAO intraperitonealy. Infarct volumes were measured 72 hr after reperfusion. Treatment with diazoxide 24 hr before the onset of ischemia exhibited a 28 % reduction (235.2±7.1 vs. 169.2± 22.5mm 3 ) and a 32 % reduction (179.6±2.0 vs.122.0±18.0mm 3 ) in infarct volumes for total brain and cortex, respectively. These findings are consistent with the assumption that delayed preconditioning is produced by the activation of mitoK ATP in the rat brain. Supported by NIH grants (HL‐30260, HL‐46558, HL‐50587, DK‐62372) for D. W. Busija.