Cilostazol, a Type III Phosphodiesterase Inhibitor, Reduces Ischemia/Reperfusion-Induced Spinal Cord Injury
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.
Conclusion: 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.
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