title: Inhibition of microRNA-29c protects the brain in a rat model of prolonged hypothermic circulatory arrest.
abstract: OBJECTIVE
  We sought to investigate the cerebroprotection of a novel microRNA mechanism by targeting peroxisome proliferator-activated receptor gamma coactivator 1-alpha in a rat model of prolonged deep hypothermia circulatory arrest.
  
  
  METHODS
  The right carotid artery and jugular vein of male Sprague-Dawley rats were cannulated for cardiopulmonary bypass. Circulatory arrest was conducted for 60 minutes when the pericranial temperature was cooled to 18°C. The sham group received the surgical procedure without cardiopulmonary bypass and deep hypothermia circulatory arrest; the deep hypothermia circulatory arrest group received cardiopulmonary bypass and deep hypothermia circulatory arrest; lentivirus control vector or lentiviral vector containing antagomiR-29c was given to the deep hypothermia circulatory arrest + vector group or the deep hypothermia circulatory arrest + antagomiR-29c group by intracerebroventricular administration 5 days before cardiopulmonary bypass (n = 8, for each of the 4 groups). Neurologic function was evaluated by the modified hole board test and beam balance task during 14 postoperative days. Expressions of caspase-3, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and miR-29c in the hippocampus were measured by Western blot and quantitative reverse transcription polymerase chain reaction. Malondialdehyde was measured using the Malondialdehyde Assay Kit (Beyotime, Jiangsu, China).
  
  
  RESULTS
  Pretreatment with antagomiR-29c significantly decreased the expression of microRNA-29c and increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha in the hippocampus (P < .05 vs deep hypothermia circulatory arrest group). The level of malondialdehyde in the hippocampus was lower in the deep hypothermia circulatory arrest + antagomiR-29c group (P < .05 vs deep hypothermia circulatory arrest group). The neurologic functions were markedly protected in rats pretreated with antagomiR-29c as evidenced by improvement of vestibulomotor and cognitive performance during the early postoperative period. In the deep hypothermia circulatory arrest + antagomiR-29c group, histologic scores of the hippocampus were improved and the level of caspase-3 in the hippocampus was lower (P < .05 vs deep hypothermia circulatory arrest group).
  
  
  CONCLUSIONS
  Inhibition of miR-29c attenuates neurologic injuries induced by prolonged deep hypothermia circulatory arrest through a peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway.
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Yongchao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China. Electronic address: cmugtx@sina.com.
authors.forename: Tianxiang
authors.initials: T
authors.lastname: Gu
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Enyi
authors.initials: E
authors.lastname: Shi
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007276:Injections, Intraventricular; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: C526366:MIRN29 microRNA, rat; D035683:MicroRNAs; D009841:Oligonucleotides; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D014157:Transcription Factors
keywords: brain; hypothermic circulatory arrest; microRNA