Dose-effects of aorta-infused clenbuterol on spinal cord ischemia-reperfusion injury in rabbits

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Abstract

Background: The β 2 adrenergic receptor (β 2 AR) plays an important role in ischemia-reperfusion (I/R) injury in various organs. Recently, a selective β 2 AR agonist clenbuterol was suggested to protect against cerebral I/R injury. This study was designed to investigate changes of β 2 ARs after spinal cord I/R injury and dose-effects of aorta-infused clenbuterol on spinal cord I/R injury in rabbits. Methods: Spinal cord ischemia was induced in New Zealand white rabbits by infrarenal abdominal aortic occlusion with a balloon catheter for 30 minutes except the sham group. During occlusion, nothing (I/R group), normal saline (NS group) or clenbuterol at different doses of 0.005, 0.01, 0.05, 0.1, 0.5, or 1 mg/kg (C 0.005 , C 0.01 , C 0.05 , C 0.1 , C 0.5 , and C 1 groups) was infused into the occluded aortic segments. The hemodynamic data, blood glucose and serum electrolytes were measured during experimental period. Neurological function was assessed according to the modified Tarlov scales until 48 hours after reperfusion. After that, the lumbar spinal cord was harvested for β 2 AR immunohistochemistry and histopathologic evaluation in the anterior horns. Results: The β 2 AR expression in the anterior horns of the spinal cord was significantly higher in the I/R group than in the sham group. Tarlov scores and the number of viable α-motor neurons were higher in C 0.01 -C 0.5 groups than in the NS group, C 0.005 and C 1 groups and were highest in the C 0.1 group. Hypotension and hyperglycemia were found in the C 1 group. Conclusion: β 2 ARs in the anterior horn were upregulated after spinal cord I/R injury. Aortic-infused clenbuterol (0.01-0.5 mg/kg) can attenuate spinal cord I/R injury dose-dependently during the ischemic period. The Optimal dosage was 0.1 mg/kg. Activation of β 2 AR could be a new therapeutic strategy for the treatment of spinal cord I/R injury. © 2013 Chen et al.

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Chen, B., Zhang, Y., Chen, L., Huang, S., Li, S., & Yao, J. (2013). Dose-effects of aorta-infused clenbuterol on spinal cord ischemia-reperfusion injury in rabbits. PLoS ONE, 8(12). https://doi.org/10.1371/journal.pone.0084095

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