Effect of the free radical scavenger MCI-186 on spinal cord reperfusion after transient ischemia in the rabbit

被引：11

作者：

Hashizume K. ^{[1
,5
]}

Ueda T. ^{[2
]}

Shimizu H. ^{[3
]}

Mori A. ^{[4
]}

Yozu R. ^{[3
]}

机构：

[1] Division of Cardiovascular Surgery, Saitama Municipal Hospital, Saitama

[2] Division of Cardiovascular Surgery, Saiseikai Utsunomiya Hospital, Utsunomiya, Tochigi

[3] Division of Cardiovascular Surgery, Keio University, Tokyo

[4] Division of Cardiac Surgery, Saitama Cardiovascular and Respiratory Center, Saitama

[5] Division of Cardiovascular Surgery, Saitama Municipal Hospital, Midori-ku, Saitama 336-8522

来源：

The Japanese Journal of Thoracic and Cardiovascular Surgery | 2005年 / 53卷 / 8期

关键词：

Animal model; Ischemia-reperfusion; Spinal cord;

D O I：

10.1007/s11748-005-0078-7

中图分类号：

学科分类号：

摘要：

Objective: Paraplegia remains a serious complication of aortic operations. The production of free radicals during reperfusion after transient ischemia is believed to induce secondary spinal neuronal injury, resulting in paraplegia. The aim of the present study was to clarify the protective effect and method of administration of antioxidants on the neurological and histological outcome in the animal model for reperfusion injury after transient spinal cord ischemia. Methods: New Zealand white rabbits underwent surgical exposure of the abdominal aorta that was clamped for 15 minutes to achieve spinal cord ischemia. Group A animals received two 10 mg/kg doses of 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186) at the time of release of the aortic clamp and 30 minutes later. In group B, MCI-186, 5 mg/kg, was given three times, at the time of aorta clamp release, 30 minutes and 12 hours later. In group C (control group), one dose of vehicle was administered. Neurological status was assessed using modified Tarlov's score until 168 hours after operation. Spinal cord sections were examined microscopically to determine the extent of ischemic neuronal damage. Results: Groups A and B animals had better neurological function than group C (p<0.001). In contrast, group C animals exhibited paraplegia or paraparesis with marked neuronal necrosis. The number of surviving neurons within examined sections of the spinal cord was significantly greater in group B than in group C (p<0.001). Conclusion: In a 15-minute ischemia-reperfusion model using rabbits, systemic repetitious administration of MCI-186, a free radical scavenger, was found to have a protective effect on the spinal cord neurons both neurologically and histologically. We postulate that the drug minimizes the delayed neuronal cell death for reperfusion injury after transient ischemia by reducing the free radical molecules. Moreover, it was thought that we could protect delayed neuronal cell death more effectively by administering MCI-186 12 hours later.

引用

页码：426 / 433

页数：7

共 30 条

[1] Svensson L.G., Crawford E.S., Hess K.R., Coselli J.S., Safi H.J., Experience with 1509 patients undergoing thoracoabdominal aortic operations, J Vasc Surg, 17, pp. 357-370, (1993)
[2] Mori A., Ueda T., Nakamichi T., Yasudo M., Aeba R., Odaguchi H., Et al., Detrimental effects of exogenous glutamate on spinal cord neurons during brief ischemia in vivo, Ann Thorac Surg, 63, pp. 1057-1062, (1997)
[3] Kirino T., Delayed neuronal death in the gerbil hippocampus following ischemia, Brain Res, 239, pp. 57-69, (1982)
[4] Moore Jr. W.M., Hollier L.H., The influence of severity of spinal cord ischemia in the etiology of delayed-onset paraplegia, Ann Surg, 213, pp. 427-432, (1991)
[5] Smith M.L., Bendek G., Dahlgren N., Rosen I., Wieloch T., Siesjo B.K., Models for studying long-term recovery following forebrain ischemia in the rat. 2. A 2-vessel occlusion model, Acta Neurol Scand, 69, pp. 385-401, (1984)
[6] Kontos H.A., George E., Brown memorial lecture. Oxygen radicals in cerebral vascular injury, Circ Res, 57, pp. 508-516, (1985)
[7] Schmidley J.W., Free radicals in central nervous system ischemia, Stroke, 21, pp. 1086-1090, (1990)
[8] Chan P.H., Schmidley J.W., Fishman R.A., Longar S.M., Brain injury, edema, and vascular permeability changes induced by oxgen-derived free radicals, Neurology, 34, pp. 315-320, (1984)
[9] Mizuno A., Umemura K., Nakashima M., Inhibitory effect of MCI-186, a free radical scavenger, on cerebral ischemia following rat middle cerebral artery occlusion, Gen Pharmacol, 30, pp. 575-578, (1998)
[10] Nishi H., Watanabe T., Sakurai H., Yuki S., Ishibashi A., Effect of MCI-186 on brain edema in rats, Stroke, 20, pp. 1236-1240, (1989)

← 1 2 3 →