title: ONO-5046 attenuation of delayed motor neuron death and effect on the induction of brain-derived neurotrophic factor, phosphorylated extracellular signal-regulated kinase, and caspase3 after spinal cord ischemia in rabbits.
abstract: OBJECTIVE
  The mechanism of spinal cord injury is believed to be related to the vulnerability of spinal motor neuron cells to ischemia. The aim of this study was to investigate whether ONO-5046, a specific inhibitor of neutrophil elastase that can attenuate tissue or organ injury in various pathologic conditions, could protect against ischemic spinal cord damage.
  
  
  METHODS
  After induction of spinal ischemia, ONO-5046 or vehicle was injected intravenously. Cell damage was analyzed by counting the number of motor neurons. To investigate the mechanism by which ONO-5046 prevents ischemic spinal cord damage, we observed the immunoreactivity of CPP32 (caspase3), brain-derived neurotrophic factor, and phosphorylated extracellular signal-regulated kinase.
  
  
  RESULTS
  ONO-5046 eased the functional deficits and increased the number of motor neurons after ischemia. The induction of caspase3 was significantly reduced by ONO-5046 treatment. Furthermore, the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal-regulated kinase were prolonged.
  
  
  CONCLUSIONS
  ONO-5046 may protect motor neurons from ischemic injury by reducing caspase3 and prolonging the expressions of brain-derived neurotrophic factor and phosphorylated extracellular signal-regulated kinase. ONO-5046 may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury.
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakurai
authors.forename: Takano
authors.initials: T
authors.lastname: Hiroshi
authors.forename: Goro
authors.initials: G
authors.lastname: Matsumiya
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects*; D010766:Phosphorylation; D011817:Rabbits; D020760:Spinal Cord Ischemia / Q000517:prevention & control*; D013449:Sulfonamides / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D013449:Sulfonamides; C069195:sivelestat; D048049:Extracellular Signal-Regulated MAP Kinases; D019272:Leukocyte Elastase; D053148:Caspase 3; D020169:Caspases; D005998:Glycine