Protective Effect Of Mitochondrial Biogenesis Induced By Curcumin In The Cerebral Ischemia Injury Of Rats

Objective：Curcumin, a natural polypheno, exerts its protective effectagainst ischemia reperfusion injury in the brain,but the underlyingmechanisms have been in debate.Mitochondria are critical intracellularorganelles in charge of cellular homeostasis.There is growing evidence tosuggest that increased mitochondrial biogenesis could rescue ischemicneurons.Hence,this study evaluated the hypothesis that curcumin couldprevent focal cerebral ischemia reperfusion injury in rats via improvedmitochondrial biogenesis.Method: Eighty adult male SD rats were randomly divided into4groups: sham-operated group, ischemia/reperfusion (I/R) group, curcumin50mg/kg+I/R (low dose) group, and curcumin100mg/kg+I/R (high dose)group. The common carotid artery, external carotid artery and internalcarotid artery on the right side were exposed in the sham-operated group.Animals from the other groups were subjected to a2-hour period of rightmiddle cerebral artery occlusion, followed by24hours of reperfusion, andthen sacrificed. Curcumin was administered (ip) in a dose of50mg/kg (lowdose group) or100mg/kg (high dose group) for5days, respectively, prior toarterial occlusion. The neurological score,the infarct volume of brain, theloss of nissl bodies and the number of mitochondria in neurons of cerebral cortex supplied by middle cerebral artery were observed,as well as theexpression of neuron-specific nuclear protein NeuN. Moreover, we detectedthe mitochondrial biogenesis regulators TFAM,NRF-1and themitochondrial protein UCP2.Result： Compared with sham-operated group, rats in I/R grouppresented focal neurological deficit, large volume of brain infarct, edema ofneurons and reduction in the number of Nissl bodies and mitochondria in thecorresponding cortical region.We also found that ischemia reperfusioninduced reduced levels of NeuN, TFAM, NRF1, and UCP2.Curcuminpreconditioning significantly improved neurological deficit, and alleviatedpathological changes in neurons and their mitochondria, along withenhanced expressions of NeuN, TFAM, NRF1,and UCP2.The abovechanges were in a dose-dependent manner.Conclusion: Our findings demonstrated that mitochondrial biogenesisplayed a protective role on cerebral ischemia reperfusion injury.Curcumininhibited the progress of cerebral ischemia reperfusion injury possiblly viaimproved mitochondrial biogenesis.