The new therapy for cerebral infarction by modulating Keap1/Neaf2 system

• Project/Area Number: 26461279
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Osaka City University (2015-2016); Keio University (2014)
• Principal Investigator: Abe Takato 大阪市立大学, 大学院医学研究科, 准教授 (30365233)
• Co-Investigator(Kenkyū-buntansha): 畝川 美悠紀 慶應義塾大学, 医学部(信濃町), 特任講師 (10548481) ; 高橋 慎一 慶應義塾大学, 医学部(信濃町), 准教授 (20236285)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: DMF / dimethylfumarate / cerebral ischemia / Nrf2 / 脳虚血 / dimethyl fumarate

Outline of Final Research Achievements

To investigate the effects of Keap1/Nrf2 system on cerebral ischemia, we tested whether dimethyl fumarate (DMF) and D-serine affect the stroke volume in mice middle cerebral artery occlusion model. DMF reduced stroke volume when it's administrated twice/day from 10 min after reperfusion. In serine racemase (SRR) null mice, in which the content of D-serine is markedly reduced, the stroke volume was significantly smaller than wild type mice.

Research Products

• [Journal Article] Cellular origin and regulation of D- and L-serine in vitro and in vivo models of cerebral ischemia. (2014)
  • Author(s): Abe T, Suzuki M, Sasabe J, Takahashi S, Unekawa M, Mashima K, Iizumi T, Hamase K, Konno R, Aiso S, Suzuki N.
  • Journal Title: J Cereb Blood Flow Metab Volume: 34(12) Issue: 12 Pages: 1928-1935
  • DOI: 10.1038/jcbfm.2014.164
  • Peer Reviewed / Open Access
• [Presentation] Cytoprotective role of microglia-derived nitric oxide induced by TLR4 stimulation in concert with astroglial pentose-phosphate pathway activation through the Keap1/Nrf2 system (2017)
  • Author(s): S. Takahashi, T. Iizumi, K. Mashima, K. Minami, Y. Izawa, T. Abe, T. Hishiki, M. Suematsu, M. Kajimura and N. Suzuki
  • Organizer: Brain 2017
  • Place of Presentation: ベルリン（ドイツ）
  • Year and Date: 2017-04-01
  • Int'l Joint Research
• [Presentation] マウス脳虚血再灌流モデルにおけるフマル酸ジメチルの神経保護効果 (2016)
  • Author(s): 南 和志、安部貴人、塚田直己、畝川美悠紀、髙橋愼一、鈴木則宏
  • Organizer: 第41回日本脳卒中学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2016-04-14
• [Presentation] MECHANISM REGULATING D-SERINE AND L-SERINE DURING TRANSIENT MIDDLE CEREBRAL ARTERY OCCLUSION IN A MOUSE MODEL (2014)
  • Author(s): T. Abe, J. Sasabe, M. Suzuki, S. Takahashi, M. Unekawa, T. Iizumi, S. Aiso, N. Suzuki.
  • Organizer: World Stroke Congress 2014
  • Place of Presentation: トルコ・イスタンブール・Halic Congress Centeｒ
  • Year and Date: 2014-10-22 – 2014-10-25