| Project/Area Number |
15K07439
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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 |
Food science
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Research Collaborator |
HATTORI Nobutaka
TANAKA Ryota
KUROKI Takuma
KURITA Naohide
NOMOTO Koji
TAKAHASHI Takuya
YAMASHIRO Yuichiro
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 脳梗塞 / 腸内細菌 / Lipopolysaccharide / トル様受容体 / 炎症 / lipopolysaccharide / 腸内細菌叢 / 急性期脳梗塞 / 糖尿病 / Toll-like receptor 4 / 自然免疫 |
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| Outline of Final Research Achievements |
We investigated the effects of the gut microbiota on acute ischemic brain injury. Fecal Enterobacteriaceae counts, plasma lipopolysaccharide (LPS) levels, and intestinal permeability were higher in db/db than in db/+ mice, which were reduced by oral administration of a non-absorbable antibiotic, polymyxin B (PL-B) in db/db mice without changing their plasma glucose levels. Infarct volume was smaller and neurological functions were better at 24 hours after cerebral ischemia in db/db mice that received PL-B compared to that in those did not. LPS and toll-like receptor (TLR) 4 were detected in the microglia, endothelial cells, and neurons at the ischemic zone border by immunohistochemistry. Levels of LPS, TLR4, inflammatory cytokines in the ischemic hemisphere were higher in db/db than in db/+ mice, which were reduced by PL-B. Our data suggest that gut dysbiosis leads to increased circulating LPS levels, thereby inducing TLR4-mediated inflammation in acute cerebral ischemia.
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