Neuroprotective Effects of Rosuvastatin in Spinal Cord Ischemia-Reperfusion Injury in Rabbits

Abstract

Background: This experimental study was performed to investigate the neuroprotective effects of rosuvastatin in a rabbit model of spinal cord ischemia-reperfusion injury. Materials and Methods: Rabbits were randomized into 3 groups of 6 animals each: group 1 (control), group 2 (ischemia), and group 3 (rosuvastatin 5 mg/kg/d). Spinal cord ischemia was produced in rabbits by a 30-minute occlusion of the aorta by clamping with aneurysm clips; just caudal to renal artery divison and above the aortic bifurcation. Rosuvastatin was administered intraperitoneally before onset of occlusion, for 3 days. At 48 hours after ischemia, neurological evaluation was performed using the Basso, Beattie, and Bresnahan locomotor rating scale before they were killed. Levels of malondialdehyde (MDA), glutathione, advanced oxidation protein products (AOPP), superoxide dismutase, catalase, nitrite/nitrate, and tumor necrosis factor-α were measured in the spinal cord tissue and plasma. Histopatologic evaluation of the tissues and activation of caspase 3 were also studied. Results: Basso, Beattie, and Bresnahan scores for rosuvastatin group were significantly higher. MDA, AOPP, and nitrite/nitrate levels in the ischemia group were significantly higher than those for control and rosuvastatin groups (P<0.05). There were no significant differences in MDA, AOPP, and nitrite/nitrate levels between rosuvastatin and control groups. In rosuvastatin group, spinal cord tissue and plasma superoxide dismutase, glutathione, and catalase levels were significantly increased compared with the ischemia group. The gross histopathologic examination demonstrated decrease in axonal damage, neuronal degeneration, and glial cell infiltration after rosuvastatin treatment. Conclusions: Rosuvastatin may protect the spinal cord tissue against ischemic damage, by its anti-inflammation and antiapoptotic effect. Although further studies including different dose regimens and time intervals are required, this drug may therefore be a good candidate for clinical use during surgical procedures on the thoracoabdominal aorta.