title: A selective inhibitor of Drp1, mdivi-1, acts against cerebral ischemia/reperfusion injury via an anti-apoptotic pathway in rats.
abstract: Mitochondrial division inhibitor (mdivi-1) is a derivative of quinazolinone that acts as a selective inhibitor of a mitochondrial fission protein Drp1. A previous study demonstrated that as a selective inhibitor of Drp1, mdivi-1 has a protective effect in an experimental model of heart ischemia/reperfusion injury. In this study, we investigated the protective effects of mdivi-1 on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that mdivi-1 (1.2mg/kg) significantly reduced cerebral damage induced by ischemia/reperfusion. This neuroprotective effect was dose-dependent. Mdivi-1 treatment blocked apoptotic cell death in cerebral ischemia/reperfusion injury, and significantly decreased the expression of Drp1 and Cytochrome C. These results suggest that mdivi-1 exerts neuroprotective effects against nerve injury after cerebral ischemia/reperfusion, and the underlying mechanism may be through the prevention of Cytochrome C release and suppression of the mitochondrial apoptosis pathway.
authors: Department of Anesthesiology, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China.
authors: Ning
authors: N
authors: Zhang
authors: Shilei
authors: S
authors: Wang
authors: Yu
authors: Y
authors: Li
authors: Lei
authors: L
authors: Che
authors: Qin
authors: Q
authors: Zhao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D034281:Dynamins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D052999:Quinazolinones / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000209:etiology / Q000473:pathology*
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D018696:Neuroprotective Agents; D052999:Quinazolinones; D012333:RNA, Messenger; D045304:Cytochromes c; C519851:Dnm1l protein, rat; D034281:Dynamins