| Project/Area Number |
16K11211
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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 |
Otorhinolaryngology
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| Research Institution | Mie University |
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Principal Investigator |
Nishida Kohei 三重大学, 医学系研究科, リサーチアソシエイト (10456733)
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| Co-Investigator(Kenkyū-buntansha) |
小林 正佳 三重大学, 医学系研究科, 准教授 (80343218)
玉利 健悟 三重大学, 教養教育院, 特任講師(教育担当) (90585176)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 嗅覚 / 鼻科学 / 再生医学 |
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| Outline of Final Research Achievements |
Refractory olfactory dysfunction is a common finding in head trauma due to olfactory nerve injury. Anti-inflammatory treatment using steroids is known to contribute to functional recovery of the central and peripheral nervous systems in injury models, while there is a concern that steroids can induce side effects. The present study examines if the inhibition of proinflammatory cytokine, high mobility group box 1 (HMGB1), can facilitate olfactory functional recovery following injury.
Anti-HMGB1 antibody-injected mice showed significantly smaller areas of injury-associated tissue, fewer astrocytes and macrophages/microglia, and an increase in regenerating nerve fibers. Both an olfactory avoidance behavioral test and evoked potential recordings showed improved functional recovery in the anti-HMGB1 antibody-injected mice. These findings suggest that inhibition of HMGB1 could provide a new therapeutic strategy for the treatment of olfactory dysfunction following head injuries.
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| Academic Significance and Societal Importance of the Research Achievements |
実地臨床において、脊髄損傷のない頭部外傷急性期のステロイド薬投与は、頭部外傷の管理、治療ガイドライン上、感染や他の副作用への懸念を理由に推奨されておらず、また、抗IL-6受容体抗体、TNF-α阻害薬は、低頻度であるものの、過剰な免疫抑制による重症感染症発症の副作用があり、より安全な薬物の探求が望まれていた。一方、抗HMGB1抗体投与による副作用はこれまでに報告がない。
今回の結果は、外傷後急性期の抗HMGB1抗体投与が嗅神経切断後の嗅神経再生促進と嗅覚機能回復に有効であることを示した。よって、この安全な抗HMGB1抗体の臨床応用は外傷性嗅覚障害の予後成績向上に貢献するものと考えられる。
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