title: Therapeutic hypothermia attenuates global cerebral reperfusion-induced mitochondrial damage by suppressing dynamin-related protein 1 activation and mitochondria-mediated apoptosis in a cardiac arrest rat model.
abstract: Therapeutic hypothermia is effective to attenuate brain ischemia/reperfusion (I/R) injury after cardiac arrest, and multiple mechanisms have been proposed. Dynamin-related protein 1 (Drp1), a large GTPases of dynamin superfamily, predominantly controls mitochondrial fission and is related to IR-induced Cyt C release and apoptosis. However, the effect of therapeutic hypothermia on Drp1 and mitochondrial fission after cardiac arrest remains still unclear. In this study, non-cardiac arrest and post-cardiac arrest rats received 6-h normothermia (37-38°C) or therapeutic hypothermia (32-34°C), and the hippocampus was harvested at 6h and 72h after cardiac arrest. Results showed the expression of Drp1 and Cyt C increased after cardiac arrest, but therapeutic hypothermia partially reversed this increase at 6h after cardiac arrest. Transmission electron microscopy (TEM) also showed a change in morphology following therapeutic hypothermia after cardiac arrest. Moreover, therapeutic hypothermia could decrease the histopathological damage, inhibit the apoptosis of CA1 neurons and improve the survival and neurological outcomes at 72h after cardiac arrest. Taken together, our study demonstrates that therapeutic hypothermia is neuroprotective against global cerebral I/R injury, which is, at least partially, ascribed to the inhibition Drp1 and Cyt C expression and the protection of mitochondrial structure.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Shenquan
authors.initials: S
authors.lastname: Cai
authors.affiliation: Jiangsu Provincial Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221000, Jiangsu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Liangbin
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Kangli
authors.initials: K
authors.lastname: Hui
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China. Electronic address: dml1200@126.com.
authors.forename: Manlin
authors.initials: M
authors.lastname: Duan
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, No. 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D045304:Cytochromes c / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D006323:Heart Arrest / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007036:Hypothermia, Induced; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D009474:Neurons / Q000473:pathology; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D045304:Cytochromes c; C519851:Dnm1l protein, rat; D034281:Dynamins
keywords: Apoptosis; Cardiac arrest; Drp1; Ischemia/reperfusion injury; Mitochondrial fission; Therapeutic hypothermia