KATP channels are present on the surface of cardiac internal membranes, skeletal muscle, brain, and mitochondrial membranes. KATP channels can be activated with selective drugs including diazoxide and cromakalim that may be able to limit ischemia-induced damage
or brain cell death. KATP channels have no relationship with a homogenous group, while other channels do not have the same combinations. This study was to characterize the effects of the neuro-protective KATP channel openers diazoxide and cromakalim in neonatal rats with
hypoxic-ischemic encephalopathy (HIE) induced by intrauterine asphyxia. Seventy-two hours-old Sprague Dawley rat pups were subjected to intrauterine asphyxia and hypoxia for 30 min, and then randomly assigned to seven groups: Vehicle, Hypoxic-ischemia (HI), Diazoxide (Dia), Cromakalim (Cro),
Diazoxide+Glibenclamide (Dia + Gli), Cromakalim+Glibenclamide (Cro + Gli), and Solvent (NaOH). Brain injury was maintained by neurologic deficit or mass injury 72 hours after HI. Moreover, gene expression of KATP channels was measured by RT-PCR 72 hours after HI. Results showed
that the hippocampus and cortex had the most serious injury after HI, next highest injury was in the cerebellum, and the least amount of injury was in the thalamus and brainstem. Diazoxide and cromakalim showed a neuroprotective effect to the five brain regions tested after intrauterine asphyxia.
The neuroprotective effect between diazoxide and cromakalim was not statistically significant and could be inhibited by glibenclamide. Diazoxide and cromakalim had the strongest neuroprotective effect in the hippocampus and cortex, which showed the most serious injury after intrauterine asphyxia.
CREB activation in the rapid, intermediate, and delayed ischemic preconditioning against hypoxic-ischemia in neonatal rat
