Protective effects against the cerebral and spinal cord injury secondary to ischemia and reperfusion by inhibition of iron-dependent lipid peroxidation

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 08457338
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: HOKKAIDO UNIVERSITY
• Principal Investigator: YASUDA Keishu Medical Hospital, Hokkaido Univ., Professor, 医学部・附属病院, 教授 (60125359)
• Co-Investigator(Kenkyū-buntansha): SASAKI Shigeyuki Medical Hospital, Hokkaido Univ., Instructor, 医学部・附属病院, 助手 (10270787)
• Project Period (FY): 1996 – 1998
• Keywords: lazaroid / 21-aminosteroids / Near-Infrared Spectrophotometry / iron-dependent lipid peroxidation / thoracic aortic surgery / paraplegia / postischemic spinal cord injury

Research Abstract

Spinal cord injury after surgical repair of the descending thoracic or thoracoabdominal aortic disease remains a persistent clinical problem.2l-aminosteroids (lazaroids) have demonstrated the protective effect against cerebral is chemic injury through the inhibition of lipidperoxidation. In the pathogenesis of is chemia-reperfusion injury the endothelium has been shown to play an important role, but little is known about whether lazaroids reduce the postischemic endothelial cell injury. We examined whether lazaroids affected the production of proinflammatory and antiinflammatory cytokines in is chemic spinal cord injury model.
Anesthetized New Zealand white rabbits underwent a 20-minute infrarenal aortic crossclamping (AXC) with pretreatment of either an intravenous 3mg/kg lazaroid U743 89G (group L ; n= 10) or the same volume saline (group P ; n=l0). Sham operation group (group 5 ; n=6) underwent only exposure of the aorta. Plasma concentrations of interleukin (IL)-8, -1b, -1 receptor antagonist (IL-1ra) and tumor necrosis factor (TNF)-a were measured at four time points. Functional assessment with Tarlov Score at 24 and 48 hours after pretreatment, pathological assessment of the spinal cord, and measurements of cytokine levels in the spinal cord were performed.
Results. 1) Plasma IL-8 and -1ra levels peaked at 1 hour after declamping. Plasma IL-8 and -1ra levels in group L were significantly lower than those in group P (*p<0.05). 2) Plasma TNFa peaked at 5 minutes after declamping, but decreased afterwards. Plasma TNFa levels were not different among three groups. 3) Spinal IL-8 levels in group L (0.98 EA 0.34 ng/g. tissue) were lower than those in group P (7.26 EA 2.26 ng/g. tissue)(*p<0.05). Spinal IL-1ra and TNFa were not significantly different. 4) Tarlov Score and pathological assessment were better in group L.
Conclusions. 1) Lazaroid U-74389G reduced the production of systemic IL-8 and -Ira and spinal IL-8 when AXC caused spinal cord injury. 2) These results indicate that lazaroids may attenuate is chemic endothelial cell injury or activation of leukocytes.