Assessment of the protective effect of nNOS inhibitor, 7-nitmindasole(7-NI) on spinal cord neurons using glutamate segmental infusion model.-Development of pharmacologic spinal cord protection for amyotrophic lateral sclerosis(ALS)
| Project/Area Number |
14571277
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | KEIO UNIVERSITY |
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Principal Investigator |
MORI Mitsuharu (2003) Keio University, School of Medicine, Instructor, 医学部, 助手 (60306610)
上田 敏彦 (2002) 慶應義塾大学, 医学部, 講師 (20138035)
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| Co-Investigator(Kenkyū-buntansha) |
森 光晴 慶應義塾大学, 医学部, 助手 (60306610)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Glutamate / Amyotrophic lateral sclerosis / 7-nitroindasole(7-NI) / nNOS inhibitor / L-NAME / Experimental model / Spinal cord protection / Glutamate segmental infusion model / n NOS inhibitor |
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| Research Abstract |
We evaluated the protective effects of nNOS inhibitor, 7-nitroindasole(7-NI) on spinal cord neurons using segmental glutamate infusion model under brief ischemia in vivo. New Zealand white rabbits underwent an infrarenal aortic isolation. Group A animals(n=7) received intraperitoneal pretreatment of nNOS inhibitor, 7-NI(25mg/kg) every two hours. Group B animals(n=7) received intraperitoneal pretreatment of non-selective NOS inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME, 25mg/kg) every two hours. Group C animals (n=7) received intravenous administration of AMPA/kainate receptor antagonist, NBQX (4.0 mg/kg) after the pretreatment similar to group A Group D animals(n=7) received oral medication of riluzole(100mg/kg/day) preoperatively for ten days. Group E(n=7) received viehcles only as a control of group A. Animals received segmental glutamate(30 mM) infusion for 6 minutes at a rate of 2ml/min. Neurologic status was scored at 12,24 and 48 hours after surgery using Tarlov score. Neurologic status was 3.9±0.7 in group A, 1.9±0.7 in group B, 3.6±1.1 in group C, 4.1±0.4 in group D and 0.9±0.7 in group E respectively. Animals in group A showed significantly better neurologic score compared with group B and group E (p<0.05). Sections from group E exhibited severe gray matter necrosis in ventral horn. In contrast, group A, group C and group D exhibited mild neuronal change with eosinophilic changes. 7-NI might have protective effects ~on spinal cord injury induced by segmental glutamate infusion combined with brief ischemia. Pharmacologic, therapy with nNOS inhibitor might be a promising strategy for ALS reducing the detrimental glutamate neurotoxicity in the spinal cord
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Report
(3 results)
Research Products
(1 results)
