A new strategy for spinal cord protection focusing on synaptic and extrasynaptic NMDA receptors
| Project/Area Number |
16K10960
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Anesthesiology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
水上 洋一 山口大学, 大学研究推進機構, 教授 (80274158)
石田 和慶 山口大学, 大学院医学系研究科, 准教授 (80314813)
若松 弘也 山口大学, 医学部附属病院, 准教授 (80379966)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 脊髄虚血 / NMDA受容体 / PSD-95 / メマンチン / 家兎 / NMDA 受容体 / PSD-95阻害薬 / ZL006 / 脊髄保護 |
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| Outline of Final Research Achievements |
Recently, it has been reported that the synaptic N-methyl-D aspartate (NMDA) receptors protect the central nervous system (CNS) against ischemic injury, whereas the extrasynaptic NMDA receptors exacerbate ischemic CNS injury. In this study, we sought to determine whether inhibition of the signaling pathways through extrasynaptic NMDA receptor protects against ischemic spinal cord injury. We investigated the protective effects of memantine and postsynaptic density protein 95 inhibitors (ZL006 and TAT-NR2B9c) on neurologic and histopathologic outcomes in a transient spinal cord ischemia model of rabbits. Our results suggest that inhibition of the signaling pathways through extrasynaptic NMDA receptors does not protect against ischemic spinal cord injury.
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| Academic Significance and Societal Importance of the Research Achievements |
胸腹部大動脈瘤手術時に起こりうる脊髄虚血による脊髄障害は患者の社会復帰に大きな影響を与える。薬物療法により脊髄を保護する方法がどこの施設でも簡単に行えるという点で最も臨床的価値が高いと考えられる。薬物による遮断あるいは活性化により保護効果の可能性があるシグナル伝達経路を一つずつ検証する地道な作業が必要である。今回の研究では、シナプス外N-methyl-D-aspartate (NMDA) 受容体の遮断による脊髄保護の可能性は低いことが判明した。
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Report
(4 results)
Research Products
(2 results)
