Spinal cord-protective effect of resorcimoline for ischemia-reperfusion injury in a rabbit model

雷索西莫林对兔模型缺血再灌注损伤的脊髓保护作用

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Abstract

OBJECTIVES: Spinal cord injury can occur after aortic surgery as a result of reactive oxygen species (ROS) generated during ischemia-reperfusion. Resorcimoline is a novel and potent antioxidant that has demonstrated ROS-scavenging activity in vitro. We evaluated the spinal cord-protective effects of resorcimoline and compared its efficacy with that of edaravone, a free-radical scavenger currently used clinically in Japan. METHODS: A spinal cord injury model was established via infrarenal aortic occlusion for 20 minutes in 30 Japanese white rabbits. The animals received saline (control), resorcimoline (6 mg/kg), or edaravone (6 mg/kg) immediately after reperfusion. Neurologic function was assessed using the modified Tarlov score, and a linear mixed model was used to analyze the modified Tarlov score data. Logistic regression analysis was used to compare the risk of paraplegia between groups. After 5 days, spinal cord segments (L3-L5) were harvested. The number of residual normal neurons was evaluated histologically, and oxidative DNA damage was assessed via immunostaining for 8-hydroxy-2-deoxyguanosine. RESULTS: Compared with the control group, resorcimoline treatment resulted in significantly greater modified Tarlov score improvement (regression coefficient; 2.025; 95% confidence interval, 0.267-3.782; P = .025), lower incidence of paraplegia (odds ratio, 0.04; 95% confidence interval, 0.002-0.4; P = .004), greater number of residual normal neurons (P = .018), and greater percentage of 8-hydroxy-2-deoxyguanosine-negative neurons (P < .001). Conversely, these parameters did not differ significantly between the edaravone and control groups. CONCLUSIONS: Resorcimoline demonstrated spinal cord-protective effects, likely associated with its antioxidant ability to eliminate ROS generated during ischemia-reperfusion.

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