Development of cerebrovascular protection therapy for neonatal hypoxic ischemic encephalopathy

• Project/Area Number: 24591601
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Osaka University
• Principal Investigator: TANIGUCHI HIDETOSHI 大阪大学, 医学(系)研究科(研究院), 招へい教員 (00622747)
• Co-Investigator(Kenkyū-buntansha): TANIIKE MASAKO 大阪大学, 連合小児発達学研究科, 教授 (30263289) ; WADA KAZUKO 大阪大学, 大学院医学系研究科, 講師 (30294094)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: プロスタグランディン / 低酸素性虚血性脳症 / iPS細胞 / 低酸素生虚血性脳症 / 新生児低酸素性虚血性脳症 / プロスタグランジン / 血管内皮細胞 / 低体温療法 / 脳血管内皮細胞 / 新生児 / 低酸素性脳症

Outline of Final Research Achievements

Hypoxic ischemic encephalopathy (HIE) in neonates is a leading cause of neurological impairment. We investigated the function of the prostaglandin in rodent models of neonatal HIE and human induced pluripotent stem cells (iPSCs). Pharmacologic activation of the EP4 receptor with a selective agonist (AE1-329) was significantly cerebroprotective through the improvement of cerebral perfusion. On the other hand, activation of EP2-4 receptors with the agonist misoprostol significantly reduced the oxidative stress in human iPSC-derived neural precursors subjected to oxygen glucose deprivation. These data indicate that the G-protein coupled EP receptors may be amenable to pharmacologic targeting in the acute setting of neonatal HIE.

Research Products

• [Journal Article] Systematic cellular disease models reveal synergistic interactions of trisomy 21 and GATA1 mutations in hematopoietic abnormalities (2016)
  • Author(s): K. Banno, S. Omori, K. Hirata, N. Nawa, N. Nakagawa, K. Nishimura, M. Ohtaka, M. Nakanishi, T. Sakuma, T. Yamamoto, T. Toki, E. Ito, T. Yamamoto, C. Kokubu, J. Takeda, H. Taniguchi, H. Arahori, K. Wada, Y. Kitabatake and K. Ozono
  • Journal Title: Cell Reports Volume: 15 Issue: 6 Pages: 1-15
  • DOI: 10.1016/j.celrep.2016.04.031
  • NAID: 120007135439
  • Peer Reviewed / Open Access
• [Journal Article] Protection by vascular prostaglandin E2 signaling in hypoxic-ischemic encephalopathy. (2014)
  • Author(s): Taniguchi H, Anacker C, Wang Q, Andreasson K
  • Journal Title: Experimental Neurology Volume: 255C Pages: 30-37
  • DOI: 10.1016/j.expneurol.2014.02.012
  • Peer Reviewed
• [Journal Article] プロスタグランジン受容体作動薬による脳血管内皮細胞保護療法 ―低酸素虚血受傷後の脳へのライフライン確保を目指す薬物治療アプローチ― (2013)
  • Author(s): 谷口英俊
  • Journal Title: 周産期学シンポジウム抄録集 Volume: 31 Pages: 55-59
• [Presentation] プロスタグランジン受容体作動薬による脳血管内皮細胞保護療法 -低酸素虚血受傷後の脳へのライフライン確保を目指す薬物治療アプローチ- (2013)
  • Author(s): 谷口英俊
  • Organizer: 第31回 周産期学シンポジウム 「成熟児のasphyxiaとcerebral palsy」
  • Place of Presentation: 大阪
• [Presentation] Cerebrovascular protection targeting EP receptors achieves infarct reduction in the model of neonatal hypoxic ischemic encephalopathy. (2012)
  • Author(s): 谷口英俊
  • Organizer: 8th Hershey Conference on Developmental Brain Injury
  • Place of Presentation: 英国