| Project/Area Number |
16K18890
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pharmacology in pharmacy
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| Research Institution | Osaka Ohtani University |
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Principal Investigator |
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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 |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | アストログリア / 頭部外傷 / 血液脳関門 / エンドセリン / ＥＴＢ受容体 / 脳浮腫 / アストロサイト / 薬理学 |
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| Outline of Final Research Achievements |
In this study, we focused on astroglia as a target of novel anti-edema drugs. Endothelin (ET) is a bioactive peptide which exerts the bioactive effects through ET receptors. As one of ET receptors, ETB receptors were mainly observed in astroglia. In traumatic brain injury (TBI) mice, cerebrovascular damage and brain edema were observed. BQ788, an ETB receptor antagonist attenuated cerebrovascular damage and brain edema in TBI mice. After TBI, excessive ascivation of astroglia was observed while BQ788 attenuated. We also confirmed that BQ788 decreased production of vascular injurious factors and increased production of vascular protective factor in TBI mice. These results suggest that BQ788 attenuates brain edema by recovery of cerebrovascular damage resulted from decrease of vascular injurious factors and increase of vascular protective factor. Thus, ETB receptor antagonist is expected to be a novel anti-edema drug by regulation of astroglial functions in future.
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| Academic Significance and Societal Importance of the Research Achievements |
脳浮腫は頭部外傷や脳血管障害などによって脳がダメージを受けた際に生じ、突然死や運動・記憶障害などの後遺症を招いてしまう致命的な病態であるが、現在、脳浮腫を根本的に治療するための薬物治療法は確立されていない。本研究成果により、ETB受容体拮抗薬が頭部外傷マウスの脳浮腫を抑制できることが示されたので、さらなる詳細な研究を続けていくことで、将来的にはETB受容体拮抗薬が新たな脳浮腫治療薬として発展することが期待される。また、ETB受容体拮抗薬は脳血管障害に対しても抑制効果を示したことから、脳卒中や脳出血に対しても応用できることも期待される。
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