Comparing Effects of Nicorandil and Dimethyl Fumarate on Stereological Parameters of the Brain in the Rat Model of Brain Ischemia

Cell death is the critical event for the pathogenic mechanism of cerebral ischemia/ reperfusion (I/R) injury. Dimethyl fumarate (DMF)has anti-inflammatory and immune-modulatory effects on cerebral ischemia and Nicorandil protects the brain against ischemic injury via its anti-inflammation and anti-apoptotic characteristics. The aim of this study was to investigate the therapeutic effects of these drugs onbehavioral and histological changes in rats’ brain after transient middle cerebral artery occlusion (MCAO( . Materials and Methods: 24 rats were randomized into four groups, including the sham, vehicle-treated I/R, DMF-treated I/R and Nicorandil-treated I/R groups withoral gavage for 3 days. Cerebral I/R injury were induced by a transient MCAO for 1 h, followed by 72 h of reperfusion. Neurobehavioral scores were evaluated for three days. Histological processing, the total and infarct volume and also numerical density and total number ofneurons, non-neurons and dead neurons in right cortex were estimated by unbiased stereological methods.Results: Although brain ischemia treatment with DMF did not have significant effect on the infarction size, it significantly improved neurobehavioral function, increased numerical density of neurons and decreased numerical density of dead neurons upon acute ischemic. However, Nicorandil treatment showed a significant reduction in the infarction volume especially in the striatum without significant effect on neurobehavioral function and numerical density of neurons, non-neurons and dead neurons. Conclusion: Although Nicorandildid not have significant effects on brain ischemia, DMF treatment supports neuronal survival and neurobehavioral improvement in ischemic stroke, while its potency is limited in the infarction size