| Project/Area Number |
15K10323
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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 | Department of Clinical Research, National Hospital Organization Kyoto Medical Center |
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Principal Investigator |
Fukuda Shunichi 独立行政法人国立病院機構(京都医療センター臨床研究センター), 糖尿病研究部, 主任研究員 (10600546)
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| Co-Investigator(Kenkyū-buntansha) |
下權谷 祐児 日本大学, 工学部, 准教授 (30552575)
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| Research Collaborator |
Ando Joji
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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 |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
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| Keywords | wall shear stress / cerebral aneurysm / P2X4 purinoceptor / CFD analysis / animal model / CFD / disturbed flow / 脳動脈瘤 / 壁ずり応力 / 動物モデル / 計算流体力学 / 乱流 / 臨床研究 / P2X4プリノセプター |
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| Outline of Final Research Achievements |
Using a P2X4 purinoceptor (involved in the blood flow sensing mechanism of cerebral endothelial cells) gene deficient mouse or the P2X4 inhibitor paroxetine in an animal model of experimentally induced cerebral aneurysms results in a significant decrease in cerebral aneurysm induction rate. The inflammatory factors known to be involved in aneurysm development were also significantly reduced.
Patient-specific geometries and flow rates of 84 cerebral aneurysms were acquired from our clinical study, the CFD ABO Study. Multivariate analyses were performed to identify associations between hemodynamic metrics and known rupture predictors (age, sex, hypertension, smoking history, location, and size). The data suggested that the differences in aneurysm rupture rate according to size and location may reflect differences in hemodynamic environments in qualitatively different ways.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、脳血管における局所的な血行力学的負荷の増大が脳動脈瘤発生のきっかけになっている可能性が示唆された。血流感知機構に関与しているP2X4の阻害剤paroxetine投与によってラット脳動脈瘤誘発率が有意に減少した。Paroxetineは抗うつ剤としてすでにヒトに使用されている安全性が担保された薬剤であり、脳動脈瘤治療薬としての臨床応用が期待される。
また、ヒト脳動脈瘤３次元画像を用いた計算流体力学的解析結果によって、血行力学的因子やこれを反映した血管構造因子が鋭敏な脳動脈瘤破裂リスク因子として利用できる可能性が示唆され、破裂予測因子としての臨床応用が期待される。
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