Neuroprotective Effect of Cyclosporin A on Spinal Cord Ischemic Injury in Rabbits

Shin, Yoon Cheol; Choe, Ghee young; Kim, Won Gon

Abstract

BACKGROUND: The purpose of this study is to ascertain the neuroprotective effect of cyclosporin A on the 25-min surgical ischemia model in the spinal cords of rabbits with neuropathological correlation and histoimmunochemical analyses. MATERIAL AND METHOD: Thirty-two New Zealand white rabbits were randomly divided into four groups: Rabbits were randomly divided into four groups: the control I2 group (n=8), the control I7 group (n=8), the cyclosporin Cs2 group (n=8), and the cyclosporin Cs7 group (n=8). The I2 group underwent a 25-min aortic cross- clamp without intervention and were sacrificed on the 2nd day postoperatively, while the I7 group underwent a 25- min of aortic cross-clamp without intervention and were sacrificed on the 7th day postoperatively. The Cs2 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25-min cross-clamp and were sacrificed on the 2nd day postoperatively, while the Cs7 group received cyclosporin A (25 mg/kg) intravenously 15 min after the 25- min cross-clamp and were sacrificed on the 7th day postoperatively. The rabbits underwent 25-min surgical aortic cross-clamp. Neurologic functions were evaluated on the 2nd day and 7th postoperative day using Tarlov scoring system. After scoring neurologic function, all rabbits were sacrificed for histopathologic observation. RESULT: All rabbits survived the experimental procedure. The values of Tarlov score did not show any differences between the control and cyclosporin groups on the 2nd day. The scores of group Cs7 (2.75+/-0.89) were significantly higher than those of group I7 (1.25+/-1.39) on the 7th day (p<0.05). On the histologic exanminations, specimens of the spinal cord showed necrosis and apoptosis. The pathologic scores of group Cs7 (1.0+/-0.53) was less than those of group I7 (2.13+/-1.36, p<0.05). TUNEL staing showed apoptosis of the specimen in group I2 and Cs2 but there was no stastically significant difference between groups on the score. There were more overexpression of HSP70 and nNOS in cyclosporine group than in control group.
CONCLUSION
We think that cyclosporin A may decrease neuronal cell death with induced upregulation of HSP70 against 25-min ischemia of the spinal cord in the rabbit.