Analysis of neuroprotective actions of astrocytes in the inflammatory tissues during cerebral infarction

• Project/Area Number: 18K14915
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Sekiya Hiroshi 東京大学, 大学院医学系研究科(医学部), 特任助教 (40511374)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: イメージング / 脳梗塞 / グリア細胞 / 神経細胞 / ATP / アストロサイト / 大脳皮質 / 視覚野

Outline of Final Research Achievements

In cerebral infarction, one of major problems is the progression of neuronal cell death in the region surrounding the infarction site, known as the penumbra, where blood flow is reduced, but the details of the pathophysiology remain unclear. In this study, a thromboembolic model that more faithfully reflects the pathophysiology was performed, and the activities of neurons and glial cells were visualized and analyzed by fluorescence imaging. Furthermore, fluorescence imaging of extracellular ATP, a gliotransmitter, was achieved, suggesting that glial cells may function to protect neurons through suppression of neuronal activity.

Academic Significance and Societal Importance of the Research Achievements

脳梗塞は、死亡原因の上位に位置し、死に至らなくても重篤な後遺症が残り得る疾患で、社会に対する負荷も重大である。しかし、脳梗塞は、ヒトを対象とした研究には困難があるなどの理由から、病態の理解は十分ではない。本研究で得られた神経細胞およびグリア細胞の活動動態や、シグナル分子であるグリオトランスミッターの細胞外動態などは、脳梗塞後の病態生理のより詳細な理解に重要であり、病態を踏まえた積極的な治療法の実現に有用であることが十分に期待される。

Research Products

• [Journal Article] In vivo Fluorescence Imaging of Extracellular ATP in the Mouse Cerebral Cortex with a Hybrid-type Optical Sensor. (2021)
  • Author(s): Kitajima N, Takikawa K, Sekiya H, Asanuma D, Sakamoto H, Namiki S, Iino M, Hirose K.
  • Journal Title: Bio Protoc. Volume: 11 Issue: 11 Pages: 1-16
  • DOI: 10.21769/bioprotoc.4046
  • Peer Reviewed / Open Access
• [Journal Article] In vivo fluorescence imaging of extracellular ATP in the mouse cerebral cortex with a hybrid-type optical sensor (2021)
  • Author(s): Nami Kitajima, Kenji Takikawa, Hiroshi Sekiya, Daisuke Asanuma, Hirokazu Sakamoto, Shigeyuki Namiki, Masamitsu Iino and Kenzo Hirose
  • Journal Title: Bio-protocol Volume: -
  • Peer Reviewed / Open Access
• [Journal Article] Real-time in vivo imaging of extracellular ATP in the brain with a hybrid-type fluorescent sensor (2020)
  • Author(s): Kitajima N, Takikawa K, Sekiya H, Satoh K, Asanuma D, Sakamoto H, Takahashi S, Hanaoka K, Urano Y, Namiki S, Iino M, Hirose K
  • Journal Title: eLife Volume: 9 Pages: 1-18
  • DOI: 10.7554/elife.57544
  • Peer Reviewed / Open Access
• [Journal Article] A three-dimensional single-cell-resolution whole-brain atlas using CUBIC-X expansion microscopy and tissue clearing (2018)
  • Author(s): Murakami Tatsuya C.、Mano Tomoyuki、Saikawa Shu、Horiguchi Shuhei A.、Shigeta Daichi、Baba Kousuke、Sekiya Hiroshi、Shimizu Yoshihiro、Tanaka Kenji F.、Kiyonari Hiroshi、Iino Masamitsu、Mochizuki Hideki、Tainaka Kazuki、Ueda Hiroki R.
  • Journal Title: Nat Neurosci Volume: 21 Issue: 4 Pages: 627-637
  • DOI: 10.1038/s41593-018-0109-1
  • Peer Reviewed
• [Journal Article] Chemical Landscape for Tissue Clearing Based on Hydrophilic Reagents. (2018)
  • Author(s): Tainaka K, Murakami TC, Susaki EA, Shimizu C, Saito R, Takahashi K, Hayashi-Takagi A, Sekiya H, Arima Y, Nojima S, Ikemura M, Ushiku T, Shimizu Y, Murakami M, Tanaka KF, Iino M, Kasai H, Sasaoka T, Kobayashi K, Miyazono K, Morii E, Isa T, Fukayama M, Kakita A, Ueda HR.
  • Journal Title: Cell Rep. Volume: 24 Issue: 8 Pages: 2196-2210
  • DOI: 10.1016/j.celrep.2018.07.056
  • NAID: 120006542018
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 脳虚血における細胞外ATP動態の生体内蛍光イメージング (2021)
  • Author(s): 北島 奈美, 瀧川 健司, 関谷 敬, 浅沼 大祐, 坂本 寛和, 並木 繁行, 飯野 正光, 廣瀬 謙造
  • Organizer: 第94回日本薬理学会年会
• [Presentation] 大脳皮質における細胞外ATP動態のin vivo蛍光イメージング (2020)
  • Author(s): 北島 奈美, 瀧川 健司, 関谷 敬, 浅沼 大祐, 坂本 寛和, 並木 繁行, 飯野 正光, 廣瀬 謙造
  • Organizer: 生理学研究所研究会
• [Presentation] 大脳皮質における細胞外ATP動態のin vivo蛍光イメージング (2019)
  • Author(s): 北島 奈美、瀧川 健司、関谷 敬、並木 繁行、飯野 正光、廣瀬 謙造
  • Organizer: 第140回日本薬理学会関東部会