title: Neuroprotective effects of autophagy induced by rapamycin in rat acute spinal cord injury model.
abstract: OBJECTIVE
  To explore the effects of rapamycin-induced autophagy on apoptosis in a rat model of acute spinal cord injury (SCI), and to explore the effect of rapamycin on apoptosis in primary spinal cord cell culture.
  
  
  METHODS
  SCI was induced at T10 in female adult Sprague-Dawley rats. After injury was induced, the rats were injected with rapamycin and/or methylprednisolone and were sacrificed at various days after injury. Apoptosis and autophagy were examined with TUNEL staining and electron microscopy. Hind limb function was assessed by the Gale scale.
  
  
  RESULTS
  The expression of the apoptosis-related protein caspase-3 did not significantly increase until 21 days following injury, while increases in LC3II and LC3I began 10 days after injury, but then declined. TUNEL staining and electron microscopy confirmed that following injury autophagy occurred before apoptosis, but by 14 days after the injury, the level of autophagy had decreased significantly while the level of apoptosis showed a continued increase. Following treatment with rapamycin, apoptosis was significantly higher than in the vehicle control group, but significantly lower than in the sham-operated group, showing a protective effect of rapamycin. Gale scale grades in rats treated with rapamycin were significantly higher compared with the vehicle control group, suggesting a functional effect of rapamycin-induced inhibition of apoptosis.
  
  
  CONCLUSIONS
  The results indicate that rapamycin significantly improved the prognosis of acute SCI in rats by inhibiting cell apoptosis. Rapamycin might be useful as a therapeutic agent for acute SCI.
authors.affiliation: Department of Orthopedics, Affiliated Union Hospital of Fujian Medical University, Fuzhou, PR China.
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Wen-Ge
authors.initials: WG
authors.lastname: Liu
authors.forename: Akram
authors.initials: A
authors.lastname: Muharram
authors.forename: Zhao-Yan
authors.initials: ZY
authors.lastname: Wu
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D046529:Microscopy, Electron, Transmission; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D018696:Neuroprotective Agents; D020123:Sirolimus