title: Inhibition of Drp1 by Mdivi-1 attenuates cerebral ischemic injury via inhibition of the mitochondria-dependent apoptotic pathway after cardiac arrest.
abstract: Mitochondrial fission is predominantly controlled by the activity of dynamin-related protein1 (Drp1), which has been reported to be involved in mitochondria apoptosis pathways. However, the role of Drp1 in a rat model of cardiac arrest remains unknown. In this study, we found that activation of Drp1 in the mitochondria was increased after cardiac arrest and inhibition of Drp1 by 1.2 mg/kg of mitochondrial division inhibitor-1 (Mdivi-1) administration after the restoration of spontaneous circulation (ROSC) significantly protected against cerebral ischemic injury, shown by the increased 72-h survival rate and improved neurological function. Moreover, the increase of the vital neuron and the reduction of cytochrome c (CytC) release, apoptosis-inducing factor (AIF) translocation and caspase-3 activation in the brain indicate that this protection might result from the suppression of neuron apoptosis. Altogether, these results indicated that Drp1 is activated after cardiac arrest and the inhibition of Drp1 is protective against cerebral ischemic injury in a rat of cardiac arrest model via inhibition of the mitochondrial apoptosis pathway.
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Emergency Medicine, People's Hospital of Baoan District, Shenzhen, China.
authors.forename: J
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Emergency Medicine, Zhongshan People's Hospital, Zhongshan, China.
authors.forename: R
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Cardiovascular Medicine, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Emergency Medicine, People's Hospital of Baoan District, Shenzhen, China.
authors.forename: M
authors.initials: M
authors.lastname: Shi
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Fang
authors.affiliation: Department of Emergency Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University, Guangzhou, China. Electronic address: syxhzt@163.com.
authors.forename: Z
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D034281:Dynamins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006323:Heart Arrest / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052999:Quinazolinones / Q000494:pharmacology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: C549041:3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone; D018696:Neuroprotective Agents; D052999:Quinazolinones; C519851:Dnm1l protein, rat; D034281:Dynamins
keywords: Drp1; Mdivi-1; apoptosis; cardiac arrest; cardiopulmonary resuscitation