title: Effects of Therapeutic Hypothermia on Apoptosis and Autophagy After Spinal Cord Injury in Rats.
abstract: METHODS
  Animal study.
  
  
  OBJECTIVE
  To further investigate the effects of therapeutic hypothermia (TH), the present study compared autophagy and apoptosis after treatment with either therapeutic moderate systemic hypothermia or methylprednisolone sodium succinate (MP) in a rat model of acute spinal cord injury (SCI).
  
  
  BACKGROUND
  The neuroprotective effects of TH have recently become an important topic in the field of SCI research.
  
  
  METHODS
  All rats were subjected to a 25-g/cm spinal cord contusion over the ninth thoracic vertebrae. After the induction of SCI, the control group did not receive any further treatment, TH group immediately received moderate systemic hypothermia for 4 hours, and MP group was administered high-dose MP. The rats were killed either 2 or 7 days after SCI, and the injured spinal cord tissues were obtained. Apoptosis and autophagy were assessed by immunohistochemical analyses and Western blot analyses. In addition, the microarchitecture of the autophagosomes was evaluated using transmission electron microscopy, and the motor activity of the rats was assessed using the Basso-Beattie-Bresnahan (BBB) locomotor rating scale.
  
  
  RESULTS
  Compared with controls, there was a significant reduction in the expression levels of cleaved caspase-8, -9, and -3 in the TH- and MP-treated groups 2 days after SCI. Moreover, compared with the control group, the expression of LC3II and Beclin-1 exhibited a significant decrease on day 2 after treatment with TH. The numbers of transferase dUTP nicked-end labeling and LC3-positive cells were significantly lower on days 2 and 7. The Basso-Beattie-Bresnahan ratings were significantly higher 6 weeks after SCI in both the TH- and MP-treated groups than in the control group.
  
  
  CONCLUSIONS
  Both TH and MP have neuroprotective effects on injured spinal cord tissues via the inhibition of apoptosis and autophagy. Thus, the application of moderate systemic hypothermia may be a useful treatment modality after acute SCI.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Orthopaedic Surgery, Jeju National University Hospital, School of Medicine, Jeju National University, Jeju, Korea; and †Department of Orthopaedic Surgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Jun-Yeong
authors.initials: JY
authors.lastname: Seo
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Jang-Woon
authors.initials: JW
authors.lastname: Kim
authors.forename: Shin-Il
authors.initials: SI
authors.lastname: Kim
authors.forename: Kee-Yong
authors.initials: KY
authors.lastname: Ha
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D001522:Behavior, Animal; D015153:Blotting, Western; D019610:Cytoprotection; D004195:Disease Models, Animal; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D008297:Male; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D009043:Motor Activity; D018696:Neuroprotective Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors
chemical_list: D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; D008776:Methylprednisolone Hemisuccinate