| Project/Area Number |
18K09084
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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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| Review Section |
Basic Section 56020:Orthopedics-related
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| Research Institution | Tokai University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
渡辺 雅彦 東海大学, 医学部, 教授 (40220925)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 脊髄損傷 / 小胞体ストレス / グルカゴン用ペプチド-1受容体作動薬 / エキセナチド / マクロファージ極性 / GLP-1受容体作動薬 / オリゴデンドロサイト前駆細胞 / オリゴデンドロサイト / アポトーシス / マクロファージ / オリゴデンドロサイト前駆細胞(OPC) |
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| Outline of Final Research Achievements |
The effects of administering the glucagon-like peptide-1 (GLP-1) receptor agonist exenatide after spinal cord injury (SCI) were examined in a rat contusion model. Compared to control animals that received PBS administration, the animals that received exenatide administration immediately after and 7 days after SCI had a significantly higher endoplasmic reticulum stress response levels along with a shift in the polarization of infiltrating macrophages leading to higher levels of anti-inflammatory M2 macrophages. The animals that received exenatide treatment did not suffer from hypoglycemia and showed significantly higher hindlimb motor function, demonstrating the therapeutic effects of exenatide for SCI.
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| Academic Significance and Societal Importance of the Research Achievements |
脊髄損傷後の再生医療では幹細胞移植が注目されているが，二次障害を軽減する薬物療法の確立はより多くの患者を救助する可能性が高いと考えられ，GLP-1受容体作動薬エキセナチド投与により脊髄損傷後の機能障害が軽減できることを確認した意義は大きい．エキセナチドは糖尿病治療薬として臨床応用されているため安全性に問題はなく，さらに糖尿病ではなくても低血糖などの副作用が発生しないことを確認した．今後その治療メカニズムをさらに解明する必要があるが，早期臨床応用に向けた確実な第一歩を踏み出せた．
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