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Reproducable Paraplegia by Thoracic Aortic Occlusion in a Murine Model of Spinal Cord Ischemia-reperfusion
Published on: March 3, 2014
Spinal cord-protective effect of resorcimoline for ischemia-reperfusion injury in a rabbit model
Yu Kawahara1, Takayuki Kawashima1, Kenshi Yoshimura1
1Department of Cardiovascular Surgery, Oita University, Oita, Japan.
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.

