Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

• Published in: International journal of experimental pathology Vol. 100; no. 5-6; pp. 337 - 349
• Main Authors: Gao, Jinbao, Wang, Haijiang, Li, Yunjun, Li, Wende
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.10.2019; John Wiley and Sons Inc
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK pathway; Animals; Apoptosis; Brain; Brain - blood supply; Brain - drug effects; Brain - metabolism; Brain - physiopathology; Cell Line; cerebral IR injury; GTP Phosphohydrolases - metabolism; Homeostasis; Homeostasis - drug effects; Hypoxia; Injuries; Ischemia; Membrane potential; Mfn1; Mice; Mitochondria; Mitochondria - drug effects; Mitochondria - pathology; Mitochondria - physiology; Mitochondrial Dynamics - drug effects; Mitochondrial Dynamics - physiology; mitochondrial stress; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Original; Oxidative stress; Pathogenesis; Reperfusion; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Resveratrol; Resveratrol - pharmacokinetics; Resveratrol - therapeutic use; Signal Transduction - drug effects; Mfn1; cerebral IR injury; AMPK pathway; mitochondrial stress; resveratrol
• ISSN: 0959-9673; 1365-2613
• DOI: 10.1111/iep.12336

Summary The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1‐mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia‐reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR‐treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1‐related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR‐treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti‐apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK‐Mfn1 pathway.