| Project/Area Number |
26670271
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Applied pharmacology
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| Research Institution | Kagawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Mayumi 九州大学, 大学院医学研究院, 助教 (80336031)
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| Co-Investigator(Renkei-kenkyūsha) |
Kobayashi Sei 山口大学, 大学院医学研究科, 教授 (80225515)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | トロンビン / 受容体 / 脱感作障害 / 内皮バリアー機能 / ミオシン軽鎖リン酸化 / 細胞内カルシウムシグナル / 蛋白質リン酸化 / 活性酸素 / 平滑筋細胞 / トロンビン受容体 / 受容体脱感作機構 / 不可逆的活性 / シグナル伝達 / 蛋白質リン酸化反応 / 酸化ストレス / 脳血管攣縮 |
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| Outline of Final Research Achievements |
Cerebral vasospasm is one of critical complications that develop after subarachnoid hemorrhage and influence vital and neurologic prognosis of the patients. The present study aims to develop innovative and ultimate strategies for the treatment of cerebral vasospasm with thrombin receptor as a therapeutic target, based on the understanding of the central mechanism of pathogenesis of vasospasm. As a result, the present research elucidated the mechanisms underlying (1) impairment of desensitization of thrombin receptor PAR1, (2) thrombin-induced endothelial barrier disruption and (3) thrombin-induced store-operated calcium influx. All these aspects play a critical role for the development of cerebral vasospasm. The findings of the present study therefore consolidated the basis for the development of a novel therapeutic strategy with PAR1 as a therapeutic target for the prevention and treatment of cerebral vasospasm.
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