title: Cilostazol, a type III phosphodiesterase inhibitor, reduces ischemia/reperfusion-induced spinal cord injury.
abstract: BACKGROUND
  Spinal cord injury is still a devastating complication after surgical repair of thoracoabdominal aortic pathologies. In this study, we investigated the protective effect of cilostazol, a type III phosphodiesterase inhibitor, against ischemia/reperfusion (I/R)-induced spinal cord injury in rats.
  
  
  METHODS
  Twenty-four rats were assigned to 3 experimental study groups: the control group (sham operation, n = 8); the ischemia group (nontreated, n = 8), which underwent aortic occlusion without pharmacologic intervention; and the cilostazol-treated group (n = 8), which received 20 mg/kg cilostazol per day orally for 3 days before spinal ischemia. All animals underwent a 45-minute period of spinal cord ischemia via clamping of the abdominal aorta between the left renal artery and the aortic bifurcation; removal of the aortic clamp was followed by reperfusion. Neurologic status was assessed before spinal ischemia and at 48 hours after the operation. All animals were sacrificed at 48 hours after the operation. Spinal cords were harvested for histopathologic examination and biochemical analyses for the malondialdehyde (MDA) level and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities.
  
  
  RESULTS
  Tarlov scores at postoperative hour 48 tended to be higher in the cilostazol-treated group than in the nontreated ischemia group (mean ± SD, 3.66 ± 0.40 versus 2.32 ± 0.80; P = .08). Spinal cord tissue MDA levels (per gram protein) were lower in the cilostazol-treated group than in the nontreated ischemia group (0.27 ± 0.01 mmol/g versus 0.33 ± 0.04 mmol/g, P = .026), and the cilostazol-treated group had higher activities of tissue SOD (519.6 ± 56.3 U/g versus 438.9 ± 67.4 U/g, P = .016) and GSH-Px (4.07 ± 1.37 U/g versus 3.21 ± 1.02 U/g, P = .47) than the nontreated ischemia group. Histopathologic analyses demonstrated that cilostazol treatment attenuated I/R-induced cellular damage.
  
  
  CONCLUSIONS
  Administration of cilostazol before spinal cord ischemia reduced neurologic injury and produced clinical improvement by attenuating oxidative stress in this rat spinal cord I/R model.
authors.affiliation: Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Sahin
authors.forename: Burak
authors.initials: B
authors.lastname: Onan
authors.forename: Adem
authors.initials: A
authors.lastname: Guler
authors.forename: Emin
authors.initials: E
authors.lastname: Oztas
authors.forename: Bülent
authors.initials: B
authors.lastname: Uysal
authors.forename: Sıddık
authors.initials: S
authors.lastname: Arslan
authors.forename: Ufuk
authors.initials: U
authors.lastname: Demirkilic
authors.forename: Harun
authors.initials: H
authors.lastname: Tatar
mesh_terms: D000818:Animals; D000077407:Cilostazol; D008297:Male; D058987:Phosphodiesterase 3 Inhibitors / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications*; D013119:Spinal Cord Injuries / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D000077407:Cilostazol