Neuroprotective effects of potassium channel openers on cerebral ischemia–reperfusion injury in diabetic rats

Abstract

ObjectivesThis study was done to estimate the potential neuroprotective role of potassium channel openers in cerebral ischemia–reperfusion (IR) injury in streptozotocin (STZ) induced type-I diabetic rats (T1DR). MethodsPotassium channel openers – cromakalim, cinnarizine and nicorandil; potassium channel blocker –glibenclamide, insulin (as an antidiabetic standard), telmisartan (as an anti-hypertensive standard agent) and vitamin E (as an antioxidant and antiapoptotic standard agent) were given for 3days in streptozotocin (45mg/kg i.v.) induced type I diabetic rats along with middle cerebral artery occlusion. After 24h of surgery, plasma glucose, neurobehavioral score, cerebral infarct volume, blood pressure and caspase-3 levels were measured to evaluate the mechanism of potassium channel openers (KCOs) for neuroprotection. ResultsFollowing STZ administration and ischemia–reperfusion, blood sugar, neurobehavioral score, cerebral infarct volume and caspase-3 levels were significantly high in diabetic-IR groups. Treatment with cromakalim, cinnarizine, nicorandil, insulin and vitamin E significantly reduce neurobehavioral score while nicorandil and vitamin E significantly reduced cerebral infarct volume. Caspase-3 levels were significantly reduced by cromakalim and nicorandil treated animals. Except insulin and glibenclamide, none of the agents significantly reduce plasma glucose levels. ConclusionTreatment of ischemic stroke with potassium channel openers in T1DR is neuroprotective. Inhibition of apoptosis may contribute to their neuroprotective effects after stroke in T1DR.