Development of novel brain protection therapy by regulating intestinal flora for ischemic brain injury
Project/Area Number |
17K09763
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurology
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Research Institution | Juntendo University |
Principal Investigator |
Urabe Takao 順天堂大学, 医学(系)研究科(研究院), 教授 (60291663)
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 腸内細菌叢 / 虚血性大脳白質損傷 / 酸化ストレス / 炎症 / 認知障害 / 脳虚血 / リポポリサッカライド / 炎症性サイトカイン / 活性化ミクログリア / 高脂肪食 / 脳神経疾患 / 脳梗塞 / 脳保護療法 |
Outline of Final Research Achievements |
In the present study, it was revealed that LPS is effluxed into the blood due to disruption of intestinal barrier function due to dysbiosis in the pathophysiology of diabetes mellitus due to chronic cerebral ischemia, resulting in metabolic endotoxemia. In addition, lipopolysaccharide (LPS) in blood acts on toll like receptor 4 (TLR4) whose expression is increased in the brain due to disruption of blood-brain barrier function due to cerebral ischemia. Moreover, activated immunocompetent cells produce inflammatory cytokines, and progresses inflammatory response. We have proved that the development of inflammatory reaction derived from dysbiosis causes onset and development of brain white matter damage.
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Academic Significance and Societal Importance of the Research Achievements |
本研究は、腸内細菌叢異常による炎症反応が虚血性脳損傷の進展に関与するメカニズムを明らかにした内容であり、学術的に意義のある成果である。 さらに、超高齢化を迎えている我が国において、脳梗塞発症のみならず認知症発症の病態に腸内細菌叢変化による炎症や酸化ストレスが関与することを示せたことは社会的にも意義が深いことである。
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Report
(4 results)
Research Products
(4 results)
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[Presentation] Gut dysbiosis promotes lipopolysaccharide-induced neuroinflammation after stroke.2019
Author(s)
N. Kurita, K. Yamashiro, R. Tanaka, Y. Ueno, N. Miyamoto, S, Nakajima, T. Urabe, Y. Yamashiro, N. Hattori
Organizer
The 29th International Symposium on Cerebral Blood Flow, Metabolism and Function (Brain & Brain PET 2019)
Related Report
Int'l Joint Research
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