Nrf2 activator attenuates brain ischemia-reperfusion injury.

• Project/Area Number: 15K19960
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Hyogo Medical University (2016); Gifu University (2015)
• Principal Investigator: Takagi Toshinori 兵庫医科大学, 医学部, 助教 (00452152)
• Research Collaborator: Hara Hideaki 岐阜薬科大学, 薬効解析学, 教授 ; Yoshimura Shinichi 兵庫医科大学, 医学部, 主任教授 ; Iwama Toru 岐阜大学, 大学院医学系研究科 脳神経外科, 教授 ; Yamauchi Keita 岐阜大学, 大学院医学系研究科 脳神経外科 ; Egashira Yusuke 岐阜大学, 大学院医学系研究科 脳神経外科 ; Imai Takahiko 岐阜薬科大学, 薬効解析学
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Nrf2 / 脳虚血再灌流障害 / 脳血液関門 / 酸化ストレス

Outline of Final Research Achievements

Bardoxylone methyl（BARD）and novel Nrf2 activator, RS-9 decreased cerebral infarction and improve neurological findings due to ischemia-reperfusion injury. In addition, BARD decreased hemorrhagic infarction and improve neurological findings under warfarin administration. BARD also attenuates hyper-permeability of blood brain barrier and ameliorates the injury of vascular endothelial cells and pericytes.
These results demonstrated the neuroprotective effects of Nrf2 activator and protection of blood brain barrier.

Research Products

• [Journal Article] Cilostazol ameliorates collagenase-induced cerebral hemorrhage by protecting the blood brain barrier (2017)
  • Author(s): Takagi T, Imai T, Mishiro K, Ishisaka M, Tsujimoto M, Ito H, Nagashima K, Matsukawa H, Tsuruma K, Shimazawa M, Yoshimura S, Kozawa O, Iwama T, Hara H.
  • Journal Title: J Cereb Blood Flow Metab. Volume: 37 Issue: 1 Pages: 123-139
  • DOI: 10.1177/0271678x15621499
  • Peer Reviewed
• [Journal Article] Nrf2 activator ameliorates hemorrhagic transformation in focal cerebral ischemia under warfarin anticoagulation (2016)
  • Author(s): Imai, T., Takagi, T., Kitashoji, A., Yamauchi, K., Shimazawa, M., Hara, H.
  • Journal Title: Neurobiology of Disease Volume: 89 Pages: 136-146
  • DOI: 10.1016/j.nbd.2016.02.001
  • Peer Reviewed
• [Journal Article] A novel nuclear factor erythroid 2-related factor 2 (Nrf2) activator RS9 attenuates brain injury after ischemia reperfusion in mice. (2016)
  • Author(s): Yamauchi K, Nakano Y,Imai T, Takagi T, Tsuruma K, Shimazawa M, Iwama T, Hara H.
  • Journal Title: Neuroscience Volume: 333 Pages: 302-10
  • DOI: 10.1016/j.neuroscience.2016.07.035
  • Peer Reviewed
• [Remarks] 岐阜大学医学部脳神経外科
  • URL: http://www.med.gifu-u.ac.jp/neurosurgery/