Therapeutic Potential of an Anti-High Mobility Group Box1 Monoclonal Antibody in Hemorrhagic stroke
Project/Area Number |
16K08909
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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 |
Applied pharmacology
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Research Institution | Okayama University |
Principal Investigator |
RYU katsuyaku 岡山大学, 医歯薬学総合研究科, 非常勤研究員 (40432637)
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Co-Investigator(Kenkyū-buntansha) |
西堀 正洋 岡山大学, 医歯薬学総合研究科, 教授 (50135943)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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Keywords | 出血性脳卒中 / 血液脳関門 / 遅発性血管攣縮 / 抗体医薬 / HMGB1 / 脳内出血 / 硬膜下出血 / 脳血管攣縮 / 脳出血 / 硬膜外出血 / 薬物治療学 |
Outline of Final Research Achievements |
High mobility group box1(HMGB1) originally identified as an architectural nuclear protein exhibits an inflammatory cytokine-like activity in the extracellular space. We showed that treatment with anti-HMGB1 monoclonal antibody (mAb) remarkably ameliorated delayed cerebral vasospasm and brain injury induced by cerebral hemorrhage in rats, even when the mAb was administered after cerebral hemorrhage. Our results indicated that anti-HMGB1 mAb efficiently inhibited the development of delayed brain injury brain through the block HMGB1 translocation and protection of blood-brain barrier (BBB) structure in the cerebral hemorrhage region.
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Academic Significance and Societal Importance of the Research Achievements |
本研究では、出血性脳障害のメカニズムに、障害によって細胞内から放出されるタンパク質HMGB1が関与することを明らかにした。更に、出血性脳障害の早期における抗HMGB1抗体の優れた治療効果が確認された。出血性脳卒中は死亡率が高く、後遺症も重篤です。特にくも膜下出血を引き起こす遅発性血管攣縮が重大な後遺症の原因となることが多い。これまで、脳内出血による神経、血管障害を抑制する薬物は開発されておらず、抗HMGB1抗体による治療法は実用化に向けた研究が期待される。
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Report
(4 results)
Research Products
(40 results)
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[Journal Article] Therapeutic potential of an anti-high mobility group box-1 monoclonal antibody in epilepsy.2017
Author(s)
Zhao J, Wang Y, Xu C, Liu K, Wang Y, Chen L, Wu X, Gao F, Guo Y, Zhu J, Wang S, Nishibori M, Chen Z.
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Journal Title
Brain Behavior and Immunity
Volume: 64
Pages: 308-319
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Metformin Directly Binds the Alarmin HMGB1 and Inhibits its Proinflammatory Activity.2017
Author(s)
Horiuchi T, Sakata N, Narumi Y, Kimura T, Hayashi T, Nagano K, Liu K, Nishibori M, Tsukita S, Yamada T, Katagiri H, Shirakawa R, Horiuchi H.
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Journal Title
J Biol Chem.
Volume: 印刷中
Issue: 20
Pages: 8436-8446
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Anti-high Mobility Group Box 1 Antibody Ameliorates Albuminuria in MRL/lpr Lupus-Prone Mice.2017
Author(s)
Watanabe H, Watanabe KS, Liu K, Hiramatsu S, Zeggar S, Katsuyama E, Tatebe N, Akahoshi A, Takenaka F, Hanada T, Akehi M, Sasaki T, Sada KE, Matsuura E, Nishibori M, Wada J.
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Journal Title
Molecular Therapy - Methods & Clinical Development
Volume: 6
Pages: 31-39
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Anti-high mobility group box-1 (HMGB1) antibody attenuates delayed cerebral vasospasm and brain injury after subarachnoid hemorrhage in rats2016
Author(s)
Haruma J, Teshigawara K, Hishikawa T, Wang D, Liu K, Wake H, Mori S, Takahashi HK, Sugiu K, Date I, Nishibori M.
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Journal Title
Scientific reports
Volume: 6
Issue: 1
Pages: 37755-37768
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Involvement of high mobility group box 1 in the development and maintenance of chemotherapy-induced peripheral neuropathy in rats2016
Author(s)
Nishida, T., Tsubota, M., Kawaishi, Y., Yamanishi, H., Kawakami, N., Sekiguchi, F., Ishikura, H., Liu, K., Nishibori, M., Kawabata, A.
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Journal Title
Toxocology
Volume: 365
Pages: 48-58
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] HMGB1 Translocation After Ischemia in the Ovine Fetal Brain.2016
Author(s)
Zhang J, Klufas D, Manalo K, Adjepong K, Davidson JO, Wassink G, Bennet L, Gunn AJ, Stopa EG, Liu K, Nishibori M, Stonestreet BS.
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Journal Title
J Neuropathol Exp Neurol.
Volume: 75(6)
Issue: 6
Pages: 527-538
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Peripheral HMGB1-induced hyperalgesia in mice: redox state-dependent distinct roles of RAGE and TLR42016
Author(s)
Yamasoba, D., Tsubota, M., Domoto, R., Sekiguchi, F., Nishikawa, H., Liu, K., Nishibori, M., Ishikura, H., Yamamoto, T., Taga, A., Kawabata, A.
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Journal Title
J. Pharmacol. Sci.
Volume: 130
Issue: 2
Pages: 139-142
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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