A new role of insulin in the protection against ischemic spinal cord injury

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591633
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Yamaguchi University
• Principal Investigator: MATSUMOTO Mishiya Yamaguchi Univ., Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (60243664)
• Co-Investigator(Kenkyū-buntansha): IIDA Yasuhiko Yamaguchi Univ., Hospital, Research Associate, 医学部附属病院, 助手 (90304485) ; YAMASHITA Atsuo Yamaguchi Univ., Hospital, Research Associate, 医学部附属病院, 助手 (50379971) ; SAKABE Takefumi Yamaguchi Univ., Graduate School of Medicine, Professor, 大学院医学系研究科, 教授 (40035225)
• Project Period (FY): 2005 – 2006
• Keywords: spinal cord ischemia / rabbit / insulin / insulin-like growth factor-1 / paraplegia

Research Abstract

The purposes of the present study were to determine whether a clinically relevant dose (0.5 IU/kg) of insulin and intrathecal insulin-like growth factor-1 (IGF-1) protect against ischemic spinal cord injury and to investigate the mechanism of the protection by the drugs. We used a rabbit spinal cord ischemia model (13 Minute ischemia). Animals were observed for 7 days after reperfusion and assessed neurologically (hindlimb motor function) and histopathologically (HE staining of the lumbar spinal cord).
In the study about insulin, we demonstrated that a relatively small dose of preischemic but not postischemic insulin that corrects mild to moderate hyperglycemia protected against ischemic spinal cord injury and that the protective effect of insulin was easily cancelled by concomitant glucose infusion that maintained blood glucose concentrations comparable to those of the untreated control group (mild hyperglycemic). These results suggest that a relatively small dose of preischemic insulin has strong protective effects and that the glycemic control is the principal mechanism for its neuroprotective effects.
In the study about IGF-1, we demonstrated that intrathecal IGF-1 administered preischemia did not protect against ischemic spinal cord injury and that intravenous administration of IGF-1 that was reported to have strong protective effects on the outcome after transient spinal cord ischemia did not show neuroprotection comparable with that study. The failure of the neuroprotection of intravenous IGF-1 may be due to the higher concentrations of blood glucose concentrations in our study than in the study that showed the neuroprotection. These results suggest that IGF-lhas, at best, minimal direct protective effects that are easily cancelled by mild hyperglycemia.