Elucidation of novel beta 1 integrin-dependent mechanisms regulating vascular permeability
| Project/Area Number |
17K16129
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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 |
Neurology
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| Research Institution | Keio University |
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Principal Investigator |
Izawa Yoshikane 慶應義塾大学, 医学部(信濃町), 講師 (90468471)
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| Research Collaborator |
TAKAHASHI Shinichi
UNEKAWA Miyuki
TSUKADA Naoki
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 血管透過性 / 血液脳関門 / タイトジャンクション / β1インテグリン / 脳血管障害 / 血管内皮細胞 / neurovascular unit / 脳出血 / 脳浮腫 / β１インテグリン / 内皮透過性 / シグナル伝達 / 神経科学 / 脳神経疾患 / 神経分子病態学 |
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| Outline of Final Research Achievements |
We investigated here the process of inducing increased permeability using a model mouse with permanent or transient ischemia, and examined whether white matter lesions in FLAIR or T2-weighted images in a human contain demyelination by a novel MR modality, Myelin-map, which can depict demyelination specifically. The results showed that microvascular permeability can increase in a few hours after the onset of ischemia, and 70kDa RITC dextran passed through the small vessels and capillaries in the ischemic core. Myelin-map showed demyelination in the white matter lesions in humans. These data suggested the possibility that leaked serum proteins, which have a molecular weight of around 70 kDa, might contribute to disruption of microvessels and damages of neuropil, observed after ischemia. These findings would provide a novel approach to the treatment of cerebral disorders including stroke and vascular dementia where the leaky vascular wall is relevant to their progression and complication.
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| Academic Significance and Societal Importance of the Research Achievements |
脳梗塞、脳出血、脳血管性認知症、そのほか様々な神経疾患において、脳血管透過性の亢進がその発症・病状悪化に関与することが知られている。しかし、脳血管透過性亢進メカニズムは十分に解明されていない。当研究により、脳虚血が細小動脈・毛細血管レベルで、血管内皮細胞の細胞内シグナル変化により血管透過性を亢進させ、血漿タンパクの漏出を誘導し、髄鞘などの実質構造を障害するという機序（仮説）に矛盾しない結果が得られた。in vitroで特定されたβ１インテグリン介在性細胞内シグナルを標的とする血管透過性制御手法は、脳血管障害、血管性認知症、そのほか血管透過性亢進が関与する神経疾患の治療確立に応用が期待される。
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Report
(3 results)
Research Products
(8 results)
