Aortic Cross-Clamping-Induced Spinal Cord Oxidative Stress in Rabbits: The Role of a Novel Antioxidant Adrenomedullin

Abstract

Spinal cord injury remains a devastating complication of thoracic and thoracoabdominal aortic operations. We aim to investigate the neuro-protective role of adrenomedullin (AM) administered to rabbits before ischemia and during reperfusion against ischemia-reperfusion (I/R) injury. Occlusion of the abdominal aorta was applied to adult rabbits, followed by removal of aortic clamp and reperfusion. The abdominal aortas of New Zealand white albino rabbits were occluded for 30 min. Experimental groups were as follows: control group (sham operation group, n = 10), I/R group (n = 9) undergoing occlusion but receiving no pharmacologic intervention, AM-treated group (n = 8) receiving 0.05 microg/kg/min AM intravenously 10 min before ischemia and during reperfusion. Neurological status was assessed at 6, 24, and 48 h after the operation. All animals were killed at 48 h after the operation. Spinal cords were harvested for histopathologic and biochemical analyses. According to Tarlov's scale, neurological status of the rabbits at postoperative hour 48 was better in the AM-treated group compared to the I/R group (P < 0.05). Decreased tissue and serum malondialdehyde levels and increased tissue and serum glutathione levels were observed in the AM-treated group (P < 0.05). In the same group tissue and serum nitrate levels were decreased (P < 0.05). Histopathologic analyses demonstrated typical morphological changes characteristic of necrosis in the I/R group. AM attenuated ischemia-induced necrosis. To our knowledge, this is the first study that shows the effects of AM administered both preischemic and during reperfusion on induced oxidative damage to injured spinal cords. AM administration may significantly reduce the incidence of spinal cord injury following temporary aortic occlusion.