Elucidation of molecular mechanism for focal brain cooling using transient receptor potential (TRP) channels
| Project/Area Number |
17K10830
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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 |
Neurosurgery
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 脳梗塞 / 局所脳冷却 / TRPV4チャネル / 細胞死 / 血液脳関門 / TRPV4チャネルアゴニスト / TRPV4チャネルアンタゴニスト / 局所脳梗塞モデルマウス / 局所脳損傷 / TRPチャネル / 脳低温療法 / TRPV4 / 頭部外傷 |
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| Outline of Final Research Achievements |
The aim of this study is to establish a focal brain cooling as a new treatment of stroke. As a result, it was clarified that the novel mechanism of anti-ischemic effects by focal brain cooling is a temperature-sensitive TRPV4 channel.
The followings are the highlights in this research. First, infarct volume in the ischemic model mice was decreased by TRPV4 antagonist or the treatment of focal brain cooling at 15℃ that inactivates TRPV4 channel. Second, the reduction of infarct volume by focal brain cooling was inhibited by TRPV4 channel agonist. Third, the infarct volume in TRPV4KO mice was decreased without the treatment of focal brain cooling. Fourth, the mechanisms of the anti-cerebral infarction were suppression of blood-brain barrier breakdown and brain cell death.
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| Academic Significance and Societal Importance of the Research Achievements |
局所脳冷却技術の臨床応用は難治性てんかんの分野で先行しているが，これまでに脳梗塞に対する局所脳冷却処置の意義を報告した例は少ない．また，局所脳冷却技術の抗脳梗塞作用機序に関しても温度制御による代謝制御および既存治療法以外の観点から解明した例はほとんどない．脳温制御による脳梗塞の制御機構が明らかになれば，温度制御による中枢疾患の制御を薬剤に代替する研究へとパラダイムシフトすることが期待できる．
血液脳関門の破綻を抑制し，かつ脳保護効果を持つ治療法および治療薬が臨床応用されれば，これまでの治療法で救えなかった脳梗塞患者を救うことが期待できる．その社会的意義は大きい．
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Report
(4 results)
Research Products
(2 results)
