Identification of the molecule initiating neural repair after ischemic stroke

• Project/Area Number: 17H05096
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Neurosurgery
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: SHICHITA Takashi 公益財団法人東京都医学総合研究所, 脳・神経科学研究分野, プロジェクトリーダー (00598443)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥25,090,000 (Direct Cost: ¥19,300,000、Indirect Cost: ¥5,790,000); Fiscal Year 2020: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2018: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2017: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: 脳卒中 / 炎症 / 神経修復 / 脳梗塞 / マクロファージ / 免疫学 / 神経化学 / ミクログリア / 脳神経 / 脳血管障害学

Outline of Final Research Achievements

Stroke is one of the common diseases which causes the disability and death, whereas therapeutic methods for stroke have not been sufficiently established. In this study, we tried to clarify the molecular and cellular mechanisms underlying sterile inflammation and neural repair after ischemic stroke. We focused on the endogenous brain factors to initiate the inflammation or neural repair. We successfully identified these molecules and next tried to develop therapeutic drugs.

Academic Significance and Societal Importance of the Research Achievements

脳卒中は本邦や先進国における主な死因、寝たきりの原因となっている。有効な治療薬の開発によって、脳卒中を起こした場合でも回復が見込めるような次世代の医療を創り出す必要がある。我々は本研究において、脳梗塞後の炎症を惹起させる新規の脳内因子の同定に成功し、このような因子を治療標的として、新たな脳卒中治療薬の開発が可能となることを証明した。さらに詳細な分子メカニズムの解明により新たな治療剤開発につなげ、次世代に脳卒中医療を創り出したいと考えている。

Research Products

• [Journal Article] Extracellular DJ-1 induces sterile inflammation in the ischemic brain. (2021)
  • Author(s): Nakamura K, Sakai S, Tsuyama J, Nakamura A, Otani K, Kurabayashi K, Yogiashi Y, Masai H, Shichita T
  • Journal Title: PLOS Biol Volume: 19 Issue: 5 Pages: e3000939-e3000939
  • DOI: 10.1371/journal.pbio.3000939
  • Peer Reviewed / Open Access
• [Journal Article] Cerebral sterile inflammation in neurodegenerative diseases. (2020)
  • Author(s): Otani K, Shichita T
  • Journal Title: Inflammation and Regeneration Volume: 40 Issue: 1 Pages: 28-28
  • DOI: 10.1186/s41232-020-00137-4
  • Peer Reviewed
• [Journal Article] Lipid mediators and sterile inflammation in ischemic stroke. (2020)
  • Author(s): Nakamura A, Otani K, Shichita T
  • Journal Title: Int Immunol Volume: in press Issue: 11 Pages: 719-725
  • DOI: 10.1093/intimm/dxaa027
  • Peer Reviewed
• [Journal Article] Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery (2019)
  • Author(s): Ito Minako、Komai Kyoko、Mise-Omata Setsuko、Iizuka-Koga Mana、Noguchi Yoshiko、Kondo Taisuke、Sakai Ryota、Matsuo Kazuhiko、Nakayama Takashi、Yoshie Osamu、Nakatsukasa Hiroko、Chikuma Shunsuke、Shichita Takashi、Yoshimura Akihiko
  • Journal Title: Nature Volume: 565 Issue: 7738 Pages: 246-250
  • DOI: 10.1038/s41586-018-0824-5
  • Peer Reviewed / Open Access
• [Journal Article] Cellular and molecular mechanisms of sterile inflammation in ischaemic stroke (2019)
  • Author(s): Nakamura Koutarou、Shichita Takashi
  • Journal Title: The Journal of Biochemistry Volume: - Issue: 6 Pages: 459-464
  • DOI: 10.1093/jb/mvz017
  • NAID: 40021920780
  • Peer Reviewed
• [Journal Article] Pivotal role of innate myeloid cells in cerebral post-ischemic sterile inflammation (2018)
  • Author(s): Jun Tsuyama, Akari Nakamura, Hiroaki Ooboshi, Akihiko Yoshimura, Takashi Shichita
  • Journal Title: Seminars in Immunopathology Volume: 40 Issue: 6 Pages: 523-538
  • DOI: 10.1007/s00281-018-0707-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Inflammation and neural repair after ischemic brain injury (2018)
  • Author(s): Sakai Seiichiro、Shichita Takashi
  • Journal Title: Neurochemistry International Volume: - Pages: 130-130
  • DOI: 10.1016/j.neuint.2018.10.013
  • Peer Reviewed
• [Journal Article] Mafb prevents excess inflammation after ischemic stroke by accelerating clearance of danger signals through MSR1. (2017)
  • Author(s): 1)Shichita T, Ito M, Morita R, Komai K, Noguchi Y, Ooboshi H, Koshida R, Takahashi S, Kodama T, Yoshimura A.
  • Journal Title: Nat Med. Volume: in press Issue: 6 Pages: 723-732
  • DOI: 10.1038/nm.4312
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Role of scavenger receptors as damage-associated molecular pattern receptors in Toll-like receptor activation. (2017)
  • Author(s): 2)Komai K, Shichita T, Ito M, Kanamori M, Chikuma S, Yoshimura A.
  • Journal Title: Int Immunol. Volume: in press Issue: 2 Pages: 59-70
  • DOI: 10.1093/intimm/dxx010
  • Peer Reviewed / Open Access
• [Presentation] The role of innate immunity and lipid metabolism in ischemic stroke (2021)
  • Author(s): Shichita T
  • Organizer: Stroke Immunology Conference
  • Int'l Joint Research / Invited
• [Presentation] Lipid metabolism and immunity in ischemic stroke. (2021)
  • Author(s): Shichita T
  • Organizer: ICBL Webinar
  • Int'l Joint Research / Invited
• [Presentation] 脳虚血後の無菌的炎症と神経修復 (2021)
  • Author(s): 七田 崇
  • Organizer: 第46回日本脳卒中学会学術集会
  • Invited
• [Presentation] 脳修復的な脂質に着目した脳卒中治療法の開発 (2020)
  • Author(s): 七田 崇
  • Organizer: 第63回日本脳循環代謝学会
  • Invited
• [Presentation] Therapeutic strategies modulating post-stroke inflammation (2020)
  • Author(s): 七田 崇
  • Organizer: 第61回日本神経学会学術大会
  • Invited
• [Presentation] Damage-associated molecular patterns in ischemic stroke. (2019)
  • Author(s): Takashi Shichita
  • Organizer: Brain 2019
  • Int'l Joint Research / Invited
• [Presentation] 脳梗塞における炎症の分子・細胞メカニズム (2019)
  • Author(s): 七田 崇
  • Organizer: 第40回日本炎症・再生医学会
  • Invited
• [Presentation] The role of innate immunity and lipid metabolism in ischemic stroke. (2019)
  • Author(s): Takashi Shichita
  • Organizer: Neuro2019
  • Invited
• [Presentation] 脳梗塞における炎症と神経修復の関連性について (2019)
  • Author(s): 七田 崇
  • Organizer: 第62回日本脳循環代謝学会
  • Invited
• [Presentation] Relationships between cerebral post-ischemic inflammation and neural repair (2019)
  • Author(s): Takashi Shichita
  • Organizer: 第48回日本免疫学会
  • Invited
• [Presentation] 脳梗塞における無菌的炎症のメカニズム (2019)
  • Author(s): 七田 崇
  • Organizer: 第44回日本脳卒中学会集会
  • Invited
• [Presentation] 脳梗塞と炎症 ～炎症は敵か？味方か？～ (2018)
  • Author(s): 七田 崇
  • Organizer: 第61回日本神経化学大会
  • Invited
• [Presentation] Sterile inflammation in ischemic stroke. (2018)
  • Author(s): Shichita T
  • Organizer: Australia-Japan Meeting on Cell Death
  • Invited
• [Presentation] Sterile inflammation induced by ischemic brain cell death (2018)
  • Author(s): Takashi Shichita
  • Organizer: 第91回日本生化学会大会
  • Invited
• [Presentation] 脳と無菌的炎症 (2018)
  • Author(s): 七田 崇、津山淳、酒井誠一郎
  • Organizer: 第41回日本神経科学大会
  • Invited
• [Presentation] Mafb prevents excess inflammation after ischemic stroke by accelerating clearance of danger signals through MSR1 (2017)
  • Author(s): Shichita T, Ooboshi H, Yoshimura A
  • Organizer: Neuroscience 2017
  • Int'l Joint Research
• [Presentation] Mafb prevents excess inflammation after ischemic stroke by accelerating clearance of danger signals through MSR1 (2017)
  • Author(s): Shichita T, Ooboshi H, Takahashi S, Kodama T, Yoshimura A
  • Organizer: Brain 2017
  • Int'l Joint Research
• [Presentation] 脳梗塞後の炎症とミクログリア・マクロファージ (2017)
  • Author(s): 七田 崇
  • Organizer: ConBio2017
  • Invited
• [Presentation] 転写因子MafbはMSR1の発現を誘導して炎症惹起因子を排除し、脳梗塞後の炎症を収束させる (2017)
  • Author(s): 七田 崇、大星博明、吉村昭彦
  • Organizer: 第60回脳循環代謝学会
• [Presentation] 転写因子MafbはMSR1の発現を誘導して炎症惹起因子を排除し、脳梗塞後の炎症を収束させる (2017)
  • Author(s): 七田 崇、吉村昭彦
  • Organizer: 第60回日本神経化学大会
• [Presentation] Regulation of cerebral post-ischemic inflammation by DAMPs (2017)
  • Author(s): Takashi Shichita
  • Organizer: 第40回日本神経科学会大会
• [Remarks] 東京都医学総合研究所 脳卒中ルネサンスプロジェクト
  • URL: http://www.igakuken.or.jp/stroke-renaiss/