Neurological Sciences

, Volume 35, Issue 11, pp 1691–1699 | Cite as

Mild hypothermia alleviates excessive autophagy and mitophagy in a rat model of asphyxial cardiac arrest

  • Jian Lu
  • Hui-Yin Qian
  • Li-Jun Liu
  • Bao-Chun Zhou
  • Yan Xiao
  • Jin-Ning Mao
  • Guo-Yin An
  • Ming-Zhong Rui
  • Tao Wang
  • Chang-Lai Zhu
Original Article

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.

Keywords

Mild hypothermia Autophagy Mitophagy Cardiac arrest Ischemic/reperfusion injury 

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Copyright information

© Springer-Verlag Italia 2014

Authors and Affiliations

  • Jian Lu
    • 1
  • Hui-Yin Qian
    • 1
  • Li-Jun Liu
    • 1
  • Bao-Chun Zhou
    • 1
  • Yan Xiao
    • 1
  • Jin-Ning Mao
    • 2
  • Guo-Yin An
    • 2
  • Ming-Zhong Rui
    • 3
  • Tao Wang
    • 4
  • Chang-Lai Zhu
    • 5
  1. 1.Department of Emergency and Critical Care MedicineThe Second Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
  2. 2.Department of CardiologyThe Second Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
  3. 3.Department of HematologyThe Second Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
  4. 4.Department of LaboratoryThe Second Affiliated Hospital of Soochow UniversitySuzhouPeople’s Republic of China
  5. 5.Electron Microscope RoomThe Affiliated Hospital of Nantong UniversityNantongPeople’s Republic of China

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