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Distribution of CCL21 and activated microglia in spinal cord-related pain

Research Project

Project/Area Number 18K09059
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionUniversity of Fukui

Principal Investigator

Hirai Takayuki  福井大学, 学術研究院医学系部門, 特別研究員 (30569132)

Co-Investigator(Kenkyū-buntansha) 中嶋 秀明  福井大学, 学術研究院医学系部門, 講師 (10397276)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脊髄損傷 / 神経障害性疼痛 / ミクログリア / マクロファージ / CCL21 / pltマウス / 活性化ミクログリア / M1/M2 phenotype / M1 / M2 / 脊髄障害性疼痛 / microglia/macrophage
Outline of Final Research Achievements

CCL21 is a chemokine that activates microglia in the central nervous system. In this study we used an SCI model in mutant (plt) mice with deficient CCL21 expression. SCI-induced hypersensitivities to mechanical and thermal stimulation were relieved in plt mice. In immunohistochemical analysis, the phenotype of microglia/macrophages was M1 type-dominant in both types of mice at the lesion site and lumbar enlargement. A decrease of M1-type microglia/macrophages was seen in plt mice, while the number of M2-type microglia/macrophages did not differ between these mice. In immunoblot analysis, expression of M1-induced cytokines was decreased in plt mice, while that of M2-induced cytokines did not differ in the two types of mice. The results indicate that suppression of expression of inflammatory cytokines by decreasing the number of M1-type microglia/macrophages at the injured site and lumbar enlargement is associated with provision of an environment for reduction of neuropathic pain.

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、CCL21が血行M1 type の遊走を惹起し、ならびに損傷部の炎症反応の増加に重要な役割を果たしていることを示唆している。 CCL21のこれらの効果は、負傷部位だけでなく、SCI高位以遠である腰膨大部に波及し、NePを誘発した可能性を示した。 これらの結果は、CCL21がSCI後のNePに重要なサイトカインでありSCI後のNePを緩和するための新しい治療法となる可能性がある。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (6 results)

All 2020 2019 2018

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Distribution and polarization of microglia and macrophages at injured sites and the lumbar enlargement after spinal cord injury2020

    • Author(s)
      Nakajima Hideaki、Honjoh Kazuya、Watanabe Shuji、Kubota Arisa、Matsumine Akihiko
    • Journal Title

      Neuroscience Letters

      Volume: 737 Pages: 135152-135152

    • DOI

      10.1016/j.neulet.2020.135152

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Relationship of Inflammatory Cytokines From M1-Type Microglia/Macrophages at the Injured Site and Lumbar Enlargement With Neuropathic Pain After Spinal Cord Injury in the CCL21 Knockout (plt) Mouse2019

    • Author(s)
      Honjoh K, Nakajima H, Hirai T, Watanabe S, Matsumine A
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 13 Pages: 525-525

    • DOI

      10.3389/fncel.2019.00525

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 脊髄損傷後の損傷部および腰膨大部におけるactivated microgliaおよびhematogenous macrophageの動態と極性2020

    • Author(s)
      窪田 有咲、中嶋 秀明、渡邉 修司、本定 和也、松峯 昭彦
    • Organizer
      第35回日本整形外科学会基礎学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Neuropathic pain after spinal cord injury relieves in CCL21 knockout (plt) mouse through decreasing of M1 type microglia/macrophage and inflammatory cytokines at the injured site and lumbar enlargement2019

    • Author(s)
      Nakajima H, Watanabe S, Honjoh K, Matsumine A
    • Organizer
      Cervical Spine Research Society European Section Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] CCL21欠損マウス脊髄損傷モデルにおけるbelow-levelの疼痛と炎症性サイトカインによるmicroglia/macrophage phenotypeの変化2018

    • Author(s)
      本定和也、中嶋秀明、高橋藍、山本悠介、出淵雄哉、松峯昭彦
    • Organizer
      第47回日本脊椎脊髄病学会
    • Related Report
      2018 Research-status Report
  • [Presentation] CCL21欠損マウス脊髄損傷モデルにおける損傷部・腰膨大部の炎症性サイトカインによるM1/M2 phenotypeの変化2018

    • Author(s)
      本定和也、中嶋秀明、高橋藍、山本悠介、出淵雄哉、松峯昭彦
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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