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

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 mul 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 mul 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.