title: Therapeutic Hypothermia Enhances Cold-Inducible RNA-Binding Protein Expression and Inhibits Mitochondrial Apoptosis in a Rat Model of Cardiac Arrest.
abstract: Therapeutic hypothermia is well known for its protective effect against brain injury after cardiac arrest, but the exact mechanism remains unclear. Cold-inducible RNA-binding protein (CIRP), a member of cold shock protein, enables mammalian cells to withstand decreased temperature by regulating gene translation. However, the role of CIRP in global cerebral ischemia after therapeutic hypothermia has not been clearly elucidated. In the present study, rats resuscitated from 4 min of cardiac arrest were separately treated with therapeutic hypothermia (immediately after return of spontaneous circulation (ROSC); targeted temperature at 33 °C) and therapeutic normothermia (targeted temperature at 36.8 °C) for 6 h. The hippocampus was harvested at 0 h (baseline), 6 h, 12 h, 1 day, 3 days, and 7 days after ROSC. The expression of CIRP messenger RNA (mRNA) was assessed by real-time PCR. CIRP and mitochondrial apoptosis-associated proteins were tested by Western blot. The histological changes and neurological function were respectively evaluated by hematoxylin-eosin staining and neurological deficit score (NDS). Compared with baseline, rats resuscitated from cardiac arrest showed increased expression of CIRP, Bax, Caspase 9, and Caspase 3 and decreased expression of Bcl-2 in hippocampus (P < 0.05). However, therapeutic hypothermia after ROSC alleviated the alterations of Bax, Caspase 9, Caspase 3, and Bcl-2, while further increased the hippocampal expression of CIRP mRNA and protein, when compared with the normothermia rats (P < 0.05). In addition, compared with the therapeutic normothermia rats, histopathological damage in CA1 zone and NDS were respectively decreased and increased in the hypothermia rats (P < 0.05). Our findings suggest that 32 °C therapeutic hypothermia exerts an important neuroprotective effects by up-regulating CIRP expression and inhibiting mitochondrial apoptosis factor production in the cardiac arrest rat model.
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China.|Jiangsu provincial Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221000, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: He-Liang
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China.
authors.forename: Kang-Li
authors.initials: KL
authors.lastname: Hui
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Xu
authors.affiliation: Jiangsu provincial Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221000, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhong
authors.affiliation: Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, China. dml1200@126.com.|Jiangsu provincial Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, 221000, China. dml1200@126.com.
authors.forename: Man-Lin
authors.identifier: 0000-0002-8079-5186
authors.initials: ML
authors.lastname: Duan
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D057773:Cold Shock Proteins and Peptides / Q000378:metabolism*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000378:metabolism* / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism; D007036:Hypothermia, Induced; D008928:Mitochondria / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D016019:Survival Analysis; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C585827:Cirbp protein, rat; D057773:Cold Shock Proteins and Peptides; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; CIRP; Cardiac arrest; Neuroprotection; Therapeutic hypothermia