Research and development of novel neuroprotective drugs targeting endothelin ETB receptor
| Project/Area Number |
15K07981
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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 |
Pharmacology in pharmacy
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| Research Institution | Kobe Pharmaceutical University (2017-2018)
Osaka Ohtani University (2015-2016) |
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Principal Investigator |
Koyama Yutaka 神戸薬科大学, 薬学部, 教授 (00215435)
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| Co-Investigator(Kenkyū-buntansha) |
道永 昌太郎 大阪大谷大学, 薬学部, 助教 (60624054)
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | エンドセリン / 脳浮腫 / アストロサイト / ETB受容体 / ＥＴＢ受容体 |
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| Outline of Final Research Achievements |
Pathophysiological roles of endothelin (ET) on brain edema and neurite extension was studied, and the following findings were obtained. 1) ETB receptor antagonist BQ 788 reduced the development of brain edema in mouse traumatic brain injury model. As for the mechanisms of anti-edema actions, BQ788 decreased the productions of astrocyte-derived brain edema factors including VEGF and MMP9. 2) The anti-brain edema action of BQ788 was examined, and it was found that it increases ANG-1 expression, which enhances the barrier function of cerebrovascular. 3) ET-1 reduced Ephrin-B1 and Ephrin-B3 expression, which are neurite outgrowth inhibitory molecules of astrocytes. This suggests that stimulation of ET receptors during brain injury may promote neurite outgrowth during neural regeneration.
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| Academic Significance and Societal Importance of the Research Achievements |
脳卒中や頭挫傷などの際に生じる脳浮腫の抑制は、患者の予後の向上に重要である。また、それら脳疾患による後遺症も、患者QOL向上のための治療法の開発が急がれている。しかし現在「脳浮腫の抑制」および「後遺障害の軽減」を意図する薬物治療は確立されていない。本研究の結果は、神経細胞を取り巻くアストログリアに多く発現するETB受容体の遮断あるいは刺激で、脳浮腫の成因となる血液脳関門の破綻の抑制や、傷害後の神経突起伸長を促し得ることを示すもので、この知見を基に新たな脳機能改善薬が開発されることが期待される。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Delayed Administration of BQ788, an ETB Antagonist, after Experimental Traumatic Brain Injury Promotes Recovery of Blood-Brain Barrier Function and a Reduction of Cerebral Edema in Mice.2018
Author(s)
Michinaga Shotaro, Kimura Akimasa, Hatanaka Shunichi, Minami Shizuho, Asano Arisa, Ikushima Yuki, Matsui Shingo, Toriyama Yoshiya, Fujii Manami, Koyama Yutaka.
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Journal Title
Journal of neurotrauma
Volume: 印刷中
Issue: 13
Pages: 1481-1494
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dysfunctional GPR40/FFAR1 signaling exacerbates pain behavior in mice.2017
Author(s)
Nakamoto K, Aizawa F, Miyagi K, Yamashita T, Mankura M, Koyama Y, Kasuya F, Hirasawa A, Kurihara T, Miyata A, Tokuyama S.
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Journal Title
PLoS One
Volume: 12(7)
Issue: 7
Pages: e0180610-e0180610
DOI
Related Report
Peer Reviewed / Open Access
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