title: Mild hypothermia alleviates excessive autophagy and mitophagy in a rat model of asphyxial cardiac arrest.
abstract: Mild hypothermia is an effective therapeutic strategy to improve poor neurological outcomes in patients following cardiac arrest (CA). However, the underlying mechanism remains unclear. The aim of the study was to evaluate the effect of mild hypothermia on intracellular autophagy and mitophagy in hippocampal neurons in a rat model of CA. CA was induced in Sprague-Dawley (SD) rats by asphyxia for 5 min. After successful resuscitation, the surviving rats were randomly divided into two groups, the normothermia (NT) group and the hypothermia (HT) group. Mild hypothermia (32 °C) was induced following CA for 4 h, and animals were rewarmed at a rate of 0.5 °C/h. Neurologic deficit scores (NDS) were used to determine the status of neurological function. Cytoplasmic and mitochondrial protein from the hippocampus was extracted, and the expression of LC3B-II/I and Parkin were measured as markers of intracellular autophagy and mitophagy, respectively. Of the 60 rats that underwent CA, 44 were successfully resuscitated (73 %), and 33 survived until the end of the experiment (55 %). Mild hypothermia maintained eumorphism of nuclear and mitochondrial structures and significantly improved NDS (p < 0.05). Expression of LC3B-II/I and Parkin in hippocampal nerve cells were significantly increased (p < 0.05) in the NT group relative to the control. Meanwhile, mild hypothermia reduced the level of LC3B-II/I and Parkin (p < 0.05) relative to the NT group. Mild hypothermia protected mitochondria and improved neurological function following CA and resuscitation after ischemia/reperfusion (I/R) injury, likely by reducing excessive autophagy and mitophagy in neurons.
authors.affiliation: Department of Emergency and Critical Care Medicine, The Second Affiliated Hospital of Soochow University, Sanxiang Road No. 1055, Suzhou, 215000, Jiangsu, People's Republic of China, 382139777@qq.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.forename: Hui-Yin
authors.initials: HY
authors.lastname: Qian
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Liu
authors.forename: Bao-Chun
authors.initials: BC
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Mao
authors.forename: Guo-Yin
authors.initials: GY
authors.lastname: An
authors.forename: Ming-Zhong
authors.initials: MZ
authors.lastname: Rui
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Chang-Lai
authors.initials: CL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000209:etiology / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology*; D007036:Hypothermia, Induced; D008297:Male; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D063306:Mitophagy / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis
chemical_list: D008869:Microtubule-Associated Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein