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The role of Zinc in the pathophysiology of spinal cord injury

Research Project

Project/Area Number 19H03771
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionOsaka University (2020-2021)
Kyushu University (2019)

Principal Investigator

Okada Seiji  大阪大学, 医学系研究科, 教授 (30448435)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥15,990,000 (Direct Cost: ¥12,300,000、Indirect Cost: ¥3,690,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords脊髄損傷 / 亜鉛 / 二次損傷 / 予後予測 / バイオマーカー / マクロファージ / 細胞生理
Outline of Research at the Start

亜鉛は生体にとって必要不可欠な微量元素の一つであり、その欠乏は皮膚症状や免疫機能の異常を引き起こすことから亜鉛シグナルは様々な細胞機能に関わっていることが知られている。しかし、脊髄損傷等の中枢神経外傷の病態に与える影響は全く解明されていない。本研究においては、亜鉛シグナルの制御が新規中枢神経外傷後の治療に繋がるかを検討する。

Outline of Final Research Achievements

In this study, we examined the role of zinc in the pathophysiology for the spinal cord injury (SCI) by using FACS and laser-microdissection. We revealed that the number of infiltrating monocytes after SCI were strongly correlated to the severity of injury and that zinc is the key factor of the inflammatory response in infiltrating monocytes, suggesting that zinc could be a useful biomarker for predicting the functional outcome. We confirmed that the acute-phase serum zinc concentration could predict the long-term functional outcome with high accuracy in both an animal experiment and a human prospective cohort study, which will help physicians determine the optimum therapeutic and rehabilitation protocols as well as evaluate the therapeutic intervention efficacy within the very acute phase. We also revealed that low serum zinc levels deteriorated the pathological and functional outcome in mice SCI model, suggesting that the zinc treatment could be the therapeutic option for SCI.

Academic Significance and Societal Importance of the Research Achievements

脊髄損傷に対する治療法が数多く研究されているが、不全麻痺であればかなりの自然回復が見られるため、どの程度が治療による効果か不明であった。我々は、血清亜鉛濃度が予後を予測できるバイオマーカーであることを明らかにすると同時に、低亜鉛状態が脊髄損傷の病態を悪化させることを解明した。これらの結果は、脊髄損傷治療研究に於いて新しい知見を与える有意義な結果であると言える。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (30 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (1 results) Journal Article (17 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 17 results,  Open Access: 7 results) Presentation (11 results) (of which Invited: 7 results) Remarks (1 results)

  • [Int'l Joint Research] CNRS(フランス国立科学研究センター)(フランス)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Microglial inflammation after chronic spinal cord injury is enhanced by reactive astrocytes via the fibronectin/β1 integrin pathway.2021

    • Author(s)
      5.Yoshizaki S, Tamaru T, Hara M, Kijima K, Tanaka M, Konno D, Matsumoto Y, Nakashima Y, Okada S.
    • Journal Title

      J Neuroinflammation

      Volume: 18 Issue: 1

    • DOI

      10.1186/s12974-020-02059-x

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reactive astrocyte nomenclature, definitions, and future directions2021

    • Author(s)
      Escartin C, Koizumi S, Verkhratsky A. et al
    • Journal Title

      Nat Neurosci

      Volume: - Issue: 3 Pages: 312-325

    • DOI

      10.1038/s41593-020-00783-4

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Metabolic Alteration in Hepatocellular Carcinoma: Mechanism of Lipid Accumulation in Well-Differentiated Hepatocellular Carcinoma2021

    • Author(s)
      Suzuki Hideo、Kohjima Motoyuki、Tanaka Masatake、Goya Takeshi、Itoh Shinji、Yoshizumi Tomoharu、Mori Masaki、Tsuda Mariko、Takahashi Motoi、Kurokawa Miho、Imoto Koji、Tashiro Shigeki、Kuwano Akifumi、Kato Masaki、Okada Seiji、Nakamuta Makoto、Ogawa Yoshihiro
    • Journal Title

      Canadian Journal of Gastroenterology and Hepatology

      Volume: 2021 Pages: 1-13

    • DOI

      10.1155/2021/8813410

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Autoreactivity of Peripheral Helper T Cells in the Joints of Rheumatoid Arthritis2021

    • Author(s)
      Sakuragi Takahide、Yamada Hisakata、Haraguchi Akihisa、Kai Kazuhiro、Fukushi Jun-ichi、Ikemura Satoshi、Akasaki Yukio、Fujiwara Toshifumi、Tsushima Hidetoshi、Tsutsui Tomoko、Kondo Masakazu、Yoshikai Yasunobu、Okada Seiji、Nakashima Yasuharu
    • Journal Title

      The Journal of Immunology

      Volume: 4 Issue: 9 Pages: 2000783-2000783

    • DOI

      10.4049/jimmunol.2000783

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Effects of prior osteoporosis treatment on 12-month treatment response of romosozumab in patients with postmenopausal osteoporosis2021

    • Author(s)
      Ebina Kosuke、Tsuboi Hideki、Nagayama Yoshio、Kashii Masafumi、Kaneshiro Shoichi、Miyama Akira、Nakaya Hiroyuki、Kunugiza Yasuo、Hirao Makoto、Okamura Gensuke、Etani Yuki、Takami Kenji、Goshima Atsushi、Miura Taihei、Nakata Ken、Okada Seiji
    • Journal Title

      Joint Bone Spine

      Volume: 88 Issue: 5 Pages: 105219-105219

    • DOI

      10.1016/j.jbspin.2021.105219

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Epidural Fat Tissue is More Effective for Scar Prevention Than Conventional Subcutaneous Fat Grafting After Laminectomy in a Mouse Model2021

    • Author(s)
      Hata Kazuhiro、Kobayakawa Kazu、Saiwai Hirokazu、Tamaru Tetsuya、Iura Hirotaka、Haruta Yohei、Ono Gentarou、Kitade Kazuki、Maeda Takeshi、Nakashima Yasuharu、Okada Seiji
    • Journal Title

      Spine

      Volume: Publish Ahead of Print Issue: 11 Pages: E485-E493

    • DOI

      10.1097/brs.0000000000004281

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term outcomes of spinal meningioma resection with outer layer of dura preservation technique2021

    • Author(s)
      Saiwai Hirokazu、Okada Seiji、Hayashida Mitsumasa、Harimaya Katsumi、Matsumoto Yoshihiro、Kawaguchi Ken-ichi、Iida Kei-ichiro、Kobayakawa Kazu、Yokota Kazuya、Maeda Takeshi、Tsuchiya Kuniyoshi、Arizono Takeshi、Saito Taichi、Nakaie Kazutoshi、Iwamoto Yukihide、Nakashima Yasuharu
    • Journal Title

      Journal of Clinical Neuroscience

      Volume: 83 Pages: 68-70

    • DOI

      10.1016/j.jocn.2020.11.026

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Shape Factor of the Spinal Cord: A Possible Predictor of Surgical Outcome for Intradural Extramedullary Spinal Tumors in the Thoracic Spine2021

    • Author(s)
      Matsumoto Yoshihiro、Saiwai Hirokazu、Iida Keiichiro、Okada Seiji、Endo Makoto、Setsu Nokitaka、Fujiwara Toshifumi、Kawaguchi Kenichi、Nakashima Yasuharu
    • Journal Title

      Global Spine Journal

      Volume: 1 Issue: 7 Pages: 098257-098257

    • DOI

      10.1177/2192568220982571

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Surgery-related predictable risk factors influencing postoperative clinical outcomes for thoracic myelopathy caused by ossification of the posterior longitudinal ligament: a multicenter retrospective study2020

    • Author(s)
      Saiwai Hirokazu、Okada Seiji、Hayashida Mitsumasa、Harimaya Katsumi、Matsumoto Yoshihiro、Kawaguchi Ken-ichi、Kobayakawa Kazu、Maeda Takeshi、Ohta Hideki、Shirasawa Kenzo、Tsuchiya Kuniyoshi、Terada Kazumasa、Kaji Kouzo、Arizono Takeshi、Saito Taichi、Fujiwara Masami、Iwamoto Yukihide、Nakashima Yasuharu
    • Journal Title

      Journal of Neurosurgery: Spine

      Volume: 32 Issue: 5 Pages: 703-709

    • DOI

      10.3171/2019.10.spine19831

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of TLR4 Signaling Inhibits Progression of Osteosarcoma by Stimulating CD8-positive Cytotoxic Lymphocytes.2020

    • Author(s)
      Yahiro K, Matsumoto Y, Yamada H, Endo M, Setsu N, Fujiwara T, Nakagawa M, Kimura M, Shimada E, Okada S, Oda Y, Nakashima Y.
    • Journal Title

      Cancer Immunol Immunother

      Volume: - Issue: 5 Pages: 745-758

    • DOI

      10.1007/s00262-020-02508-9

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The beneficial aspects of spasticity in relation to ambulatory ability in mice with spinal cord injury2019

    • Author(s)
      Yoshizaki Shingo、Yokota Kazuya、Kubota Kensuke、Saito Takeyuki、Tanaka Masatake、Konno Dai-jiro、Maeda Takeshi、Matsumoto Yoshihiro、Nakashima Yasuharu、Okada Seiji
    • Journal Title

      Spinal Cord

      Volume: - Issue: 5 Pages: 537-543

    • DOI

      10.1038/s41393-019-0395-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Features of Liver Injury Induced by Immune Checkpoint Inhibitors in Japanese Patients2019

    • Author(s)
      Imoto Koji、Kohjima Motoyuki、Hioki Tomonobu、Kurashige Tomoyuki、Kurokawa Miho、Tashiro Shigeki、Suzuki Hideo、Kuwano Akifumi、Tanaka Masatake、Okada Seiji、Kato Masaki、Ogawa Yoshihiro
    • Journal Title

      Canadian Journal of Gastroenterology and Hepatology

      Volume: 2019 Pages: 1-12

    • DOI

      10.1155/2019/6391712

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Post-carbon-ion radiotherapy vertebral pathological fractures in upper cervical primary malignant spinal tumors treated by occipito-cervical fusion2019

    • Author(s)
      Baba Satoshi、Matsumoto Yoshihiro、Kawaguchi Kenichi、Iida Keiichiro、Saiwai Hirokazu、Okada Seiji、Matsunobu Akira、Shioyama Yoshiyuki、Nakashima Yasuharu
    • Journal Title

      Archives of Orthopaedic and Trauma Surgery

      Volume: 印刷中 Issue: 11 Pages: 1525-1531

    • DOI

      10.1007/s00402-019-03183-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical results of carbon-ion radiotherapy with separation surgery for primary spine/paraspinal sarcomas.2019

    • Author(s)
      Matsumoto Y, Matsunobu A, Kawaguchi K, Hayashida M, Iida K, Saiwai H, Okada S, Endo M, Setsu N, Fujiwara T, Baba S, Nomoto S, Nakashima Y.
    • Journal Title

      Int J Clin Oncol

      Volume: 24 Issue: 11 Pages: 1490-1497

    • DOI

      10.1007/s10147-019-01505-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tranexamic acid reduces heme cytotoxicity via the TLR4/TNF axis and ameliorates functional recovery after spinal cord injury2019

    • Author(s)
      Yoshizaki Shingo、Kijima Ken、Hara Masamitsu、Saito Takeyuki、Tamaru Tetsuya、Tanaka Masatake、Konno Dai-jiro、Nakashima Yasuharu、Okada Seiji
    • Journal Title

      Journal of Neuroinflammation

      Volume: 16 Issue: 1

    • DOI

      10.1186/s12974-019-1536-y

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prone position surgery for a professional sumo wrestler with thoracic ossification of the posterior longitudinal ligament resulting in intraoperative brachial plexus injury by hypertrophic pectoral muscles2019

    • Author(s)
      Saiwai Hirokazu、Okada Seiji、Kawaguchi Ken-ichi、Saito Takeyuki、Hayashida Mitsumasa、Matsushita Akinobu、Matsumoto Yoshihiro、Nakashima Yasuharu
    • Journal Title

      Journal of Clinical Neuroscience

      Volume: 63 Pages: 227-230

    • DOI

      10.1016/j.jocn.2019.01.047

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Macrophage centripetal migration drives spontaneous healing process after spinal cord injury2019

    • Author(s)
      Kobayakawa K、Ohkawa Y、 Yoshizaki S、T、Saito T、Kijima Ken、Yokota K、Hara M、Kubota K、Matsumoto Y、Harimaya K、Ozato K、Masuda T、Tsuda M、Tamura T、Inoue K、Edgerton V. R、Iwamoto Y、Nakashima Y、Okada S
    • Journal Title

      Science Advances

      Volume: 5 Issue: 5

    • DOI

      10.1126/sciadv.aav5086

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 整形外科研究の新時代2022

    • Author(s)
      岡田誠司
    • Organizer
      兵庫県整形外科医会学術講演
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 脊髄損傷の予後予測2021

    • Author(s)
      岡田誠司
    • Organizer
      第94回日本整形外科学会学術総会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 整形外科医にしかできない基礎研究2021

    • Author(s)
      岡田誠司
    • Organizer
      第36回日本整形外科学会基礎学術集会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 整形外科医のサイエンス2021

    • Author(s)
      岡田誠司
    • Organizer
      第14回岡山運動器フォーラム
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 脊椎脊髄外科のサイエンス2021

    • Author(s)
      岡田誠司
    • Organizer
      Orthopaedics Expert Seminar in Sendai
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] 脊髄再生研究の現状と課題2021

    • Author(s)
      岡田誠司
    • Organizer
      千里ライフサイエンス新適塾
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脊椎脊髄疾患のサイエンス2020

    • Author(s)
      岡田誠司
    • Organizer
      沖縄整形外科研修会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 脊髄損傷後慢性期の損傷部瘢痕除去は、治癒過程を再開させ、治療介入が再び可能となる2019

    • Author(s)
      吉崎 真吾, 貴島 賢, 田丸 哲弥, 田中 正剛, 今野 大治郎, 中島 康晴, 岡田 誠司
    • Organizer
      第34回 日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脊髄損傷慢性期における瘢痕形成アストロサイトの特性の解明2019

    • Author(s)
      田丸哲弥, 吉崎真吾, 畑和宏, 井浦広貴, 岡田誠司, 中島康晴
    • Organizer
      第34回 日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 関節拘縮におけるペリオスチンの役割2019

    • Author(s)
      井浦 広貴, 岡田 誠司, 貴島 賢, 吉崎 真吾, 畑 和宏, 田丸 哲弥, 中島 康晴
    • Organizer
      第34回 日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脊髄損傷後急性期トラネキサム酸投与による運動機能改善メカニズムの解明2019

    • Author(s)
      吉崎 真吾, 岡田 誠司, 中島 康晴
    • Organizer
      第38回日本運動器移植・再生医学研究会
    • Related Report
      2019 Annual Research Report
  • [Remarks] definition of reactive astrocytes

    • Related Report
      2020 Annual Research Report

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Published: 2019-04-18   Modified: 2023-01-30  

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