| Project/Area Number |
24390061
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
DATE Isao 岡山大学, 大学院医歯薬学総合研究科, 教授 (70236785)
TAKAHASI Hideo 近畿大学, 医学部, 教授 (60335627)
RYU Katsuyaku 岡山大学, 大学院医歯薬学総合研究科, 助教 (40432637)
WAKE Hidenori 岡山大学, 大学院医歯薬学総合研究科, 助教 (60570520)
TESHIGAWARA Kiyoshi 岡山大学, 大学院医歯薬学総合研究科, 助教 (40403737)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
Fiscal Year 2014: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2013: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2012: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
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| Keywords | HMGB1 / 脳外傷 / グリチルリチン / 脊髄損傷 / 血液脳関門 / ミクログリア / 抗体医薬 / 脳腫瘍 |
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| Outline of Final Research Achievements |
Fluid-percussion-induced injury on the brain was produced in rats. The increase in blood-brain barrier permeability and resulting brain edema was detected in the penumbra area. The HMGB1 translocation from nuclei to extracellular space was observed in neurons in injured region. BBB disruption, activation of microglia, and the increase in the expression of inflammatory cytokines were observed in the same region. The treatment with anti-HMGB1 mAb inhibited the inflammatory response induced by injury by 85%, associated with the improvement of neurological symptoms. Glycyrrhizin, an active constituent of licorice that binds to HMGB1, produced a similar activity to anti-HMGB1 mAb. The inhibitory effects of glycyrrhizin on traumatic brain injury was not observed in RAGE knockout mice, suggesting the involvement of RAGE in the action of HMGB1 released from neurons. Similarly, anti-HMGB1 mAb improved the paralysis of hind limb dramatically due to the prevention of blood-spinal cord barrier.
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