| Project/Area Number |
18K16728
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56030:Urology-related
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| Research Institution | University of Fukui |
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Principal Investigator |
Yamauchi Hiroki 福井大学, 学術研究院医学系部門, 特別研究員 (40464086)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 脊髄損傷 / 排尿障害 / グルタミン酸 / ＮＭＤＡ / 神経可塑性 / 神経因性膀胱 / 排尿筋括約筋協調不全 / NMDA / 脊髄 / 膀胱 |
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| Outline of Final Research Achievements |
Detrusor-urethral sphincter dyssynergia (DSD) is observed in supranuclear spinal cord injury, causing renal failure from upper urinary tract dysfunction. It is possible that the lower urinary tract undergo neuro-plastic changes through the spinal cord via glutamate receptors NMDA (N-methyl-D-aspartate)in the development of DSD. The spinal cord was cut at the Th8 levelin 8-week-old SD female rats, and Dizocilpin (an NMDA receptor antagonist) was intraperitoneally administered at various times after the cutting to see the influence on DSD. As a result, NMDA receptors are involved in the development of non-voiding bladder contraction.Inhibition of NMDA receptors for 1 week after spinal cord injury may become treatment strategy in patients with spinal cord injury. Since NMDA receptors antagonist also improves micturition efficiency, it is likely to be involved in the occurrence of DSD.
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| Academic Significance and Societal Importance of the Research Achievements |
脊髄損傷では尿排出障害や尿失禁などの下部尿路機能障害は必発で、障害が継続すると腎不全を惹起する。下部尿路機能障害には排尿筋外尿道括約筋協調不全がみられるが、これを治療することはこれまで困難とされてきた。そこで雌性ラットに脊髄損傷由来の排尿筋外尿道括約筋協調不全を作成し、グルタミン酸受容体の１つNMDA (N-methyl-D-aspartate)受容体の役割について検討を行った。その結果、脊髄損傷受傷後1週間NMDA受容体を遮断する薬剤を投与すると膀胱の異常な収縮の発生が抑制され、残尿も少なくて排尿効率が良いことが確認された。NMDA受容体遮断は脊髄損傷患者の治療に繋がる可能性がある。
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