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

Abstract

BACKGROUND: The β2 adrenergic receptor (β2AR) plays an important role in ischemia-reperfusion (I/R) injury in various organs. Recently, a selective β2AR agonist clenbuterol was suggested to protect against cerebral I/R injury. This study was designed to investigate changes of β2ARs 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 (C0.005, C0.01, C0.05, C0.1, C0.5, and C1 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 β2AR immunohistochemistry and histopathologic evaluation in the anterior horns. RESULTS: The β2AR 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 C0.01-C0.5 groups than in the NS group, C0.005 and C1 groups and were highest in the C0.1 group. Hypotension and hyperglycemia were found in the C1 group. CONCLUSION: β2ARs 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 β2AR could be a new therapeutic strategy for the treatment of spinal cord I/R injury.