title: Citicoline and postconditioning provides neuroprotection in a rat model of ischemic spinal cord injury.
abstract: BACKGROUND
  Ischemic spinal cord injury is a chain of events caused by the reduction and/or cessation of spinal cord blood flow, which results in neuronal degeneration and loss. Ischemic postconditioning is defined as a series of intermittent interruptions of blood flow in the early phase of reperfusion and has been shown to reduce the infarct size in cerebral ischemia. Our study aimed to characterize the relationship between the neuronal injury-decreasing effects of citicoline and ischemic postconditioning, which were proven to be effective against the apoptotic process.
  
  
  METHODS
  Spinal cord ischemia was produced in rats using an intrathoracic approach to implement the synchronous arcus aorta and subclavian artery clipping method. In our study, 42 male Sprague-Dawley rats (309 +/- 27 g) were used. Animals were divided into sham operated, spinal ischemia, citicoline, postconditioning, and postconditioning citicoline groups. Postconditioning was generated by six cycles of 1 min occlusion/5 min reperfusion. A 600 mmol/kg dose of citicoline was given intraperitoneally before ischemia in the citicoline and postconditioning citicoline groups. All rats were sacrificed 96 h after reperfusion. For immunohistochemical analysis, bcl-2, caspase 3, caspase 9, and bax immune staining were performed. Caspase 3, caspase 9, bax, and bcl-2 were used as apoptotic and antiapoptotic markers, respectively.
  
  
  RESULTS
  The blood pressure values obtained at the onset of reperfusion were significantly lower than the preischemic values. A difference in immunohistochemical scoring was detected between the caspase 3, caspase 9, bax, and bcl-2 groups. When comparisons between the ischemia (groups 2, 3, 4, and 5) and sham groups (group 1) were performed, a significant increase in caspase 3, caspase 9, bax, and bcl-2 was detected. When comparing the subgroups, the average score of caspase 9 was found to be significantly higher in ischemia group 2. The average score of bcl-2 was also found to be significantly higher in postconditioning and citicoline group 5.
  
  
  CONCLUSIONS
  It is thus thought that combining citicoline with postconditioning provides protection by inhibiting the caspase pathway and by increasing the antiapoptotic proteins.
authors.affiliation: Department of Neurosurgery, Uludag University School of Medicine, 16059 Bursa, Turkey.
authors.forename: Alper
authors.initials: A
authors.lastname: Turkkan
authors.forename: Tulin
authors.initials: T
authors.lastname: Alkan
authors.forename: Bulent
authors.initials: B
authors.lastname: Goren
authors.forename: Hasan
authors.initials: H
authors.lastname: Kocaeli
authors.forename: Eylem
authors.initials: E
authors.lastname: Akar
authors.forename: Ender
authors.initials: E
authors.lastname: Korfali
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004789:Enzyme Activation / Q000502:physiology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D020760:Spinal Cord Ischemia / Q000473:pathology / Q000503:physiopathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D018697:Nootropic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003566:Cytidine Diphosphate Choline; D019870:1-Phosphatidylinositol 4-Kinase; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9