Nicorandil Effects on the Acute Brain Ischemia in MCAO-Induced Stroke Rat Model

Stroke is the second leading cause of death worldwide. There is no effective and generally accepted treatment for the acute ischemic stroke except thrombolysis with recombinant tissue plasminogen activator that has many limitations. Nicorandil, a potassium ATP channel opener, decreases inflammation and prevents cell death. The aim of this study was to evaluate nicorandil effects on the acute brain ischemia. Materials and Methods: 28 male Sprague Dawley rats weighing 200-250g were randomly divided into four groups: the sham group that tolerated anesthesia and surgery without middle cerebral artery occlusion (MCAO) and drug or vehicle. The control, nicorandil 1 and 3mg/kg groups underwent MCAO and received nicorandil solvent, nicorandil 1 and 3mg/kg intraperitoneally, respectively.The behavioral recovery of rats was evaluated using Garcia score test. The ischemic size, the numerical density of neuron and dead neuron in cortex, striatum andhippocampus calculated by using stereological methods. Results: Behavioral tests showed that nicorandil improved neurological functions. Although nicorandil did not show significant changes in the brain total volume, it significantly decreased ischemic size that was more obviousin higher dose. Furthermore, the numerical density of neurons in treatment groups was significantly higher than the control group in higher dose and numerical density of dead neurons in treatment groups was significantly lower than the control group. Conclusion: Nicorandilimproved not only the sensory and motor behaviors, but also it reduced ischemic size and these improvements were dose dependent. It also increased neuronal number in different parts of the brain and reduced number of dead neurons. Furthermore, the neurological improvementswere correlated with histological findings. These results may show neuroprotective and anti-apoptotic effects of this drug, but it did not support its anti-inflammatory effect, at least in the acute phase of brain ischemia.