| Project/Area Number |
20591688
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Ehime University |
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Principal Investigator |
HATA Ryuji Ehime University, 大学院・医学系研究科, 准教授 (90258153)
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| Co-Investigator(Kenkyū-buntansha) |
ONISHI Takanori 愛媛大学, 大学院・医学系研究科, 教授 (70233210)
KUMON Yoshiaki 愛媛大学, 大学院・医学系研究科, 准教授 (80127894)
DEZAKI Junzo 愛媛大学, 大学院・医学系研究科, 講師 (00036451)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 脳虚血 / 自然免疫 / TLR4(Toll like receptor 4) / マイクログリア / TLR4 (Toll like receptor 4) / キメラマウス / TLR4 |
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| Research Abstract |
Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs). Among them, TLR4 recognizes primarily lipopolysaccharide (LPS) and an increasing evidence points that TLR4 plays a crucial role in the concert mechanism of the cerebra ischemia. In this study, we investigated the effect of targeted disruption of TLR4 on the severity of ischemic brain injury. TLR4 ablation significantly decreased infarct size at 1 day after reperfusion. The amelioration of tissue damage in the absence of TLR4 underscores the importance of innate immunity for the manifestation of ischemic brain injury. Furthermore, TLR4 ablation in the bone marrow derived macrophage significantly decreased infarct size. These results indicate that bone barrow derived macrophages are an important modulator of ischemic brain injury.
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