Tissue remodeling by microglia for a novel therapeutic strategy in chronic cerebral ischemia

• Project/Area Number: 25860702
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurology
• Research Institution: Niigata University
• Principal Investigator: KANAZAWA Masato 新潟大学, 医歯学総合病院, 助教 (80645101)
• Co-Investigator(Renkei-kenkyūsha): SHIMOHATA Takayoshi 新潟大学, 脳研究所, 准教授 (60361911) ; TAKAHASHI Tetsuya 新潟大学, 医歯学総合病院, 助教 (20515663)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脳虚血 / 細胞療法 / ミクログリア / 組織リモデリング / 血管リモデリング / 脳梗塞 / VEGF / サイトカイン / 慢性期 / 細胞移植療法

Outline of Final Research Achievements

We evaluated the cellular proliferation in rats subjected to focal cerebral ischemia. We observed proliferated endothelial cells and pericytes, and increased numbers of microglia even though in the ischemic core, and angiogensis in the peripheral zone of the ischemic core at 7 and 14 days after cerebral ischemia. In vitro primary cells revealed that vascular endothelial growth factor was secreted from the microglia after oxygen-glucose deprivation (OGD). Protective growth factor progranulin was also secreted from the neuronal cells and microglia after OGD. Finally, we demonstrated the therapeutic potential of microglia against chronic focal cerebral ischemia. Seven days after ischemia, intraarterial injection of microglia stimulated OGD via carotid artery improved motor outcome compared to injections of astrocytes and phosphate buffer solution. Microglial transplantation may be a novel therapeutic strategy that provides tissue remodeling after chronic cerebral ischemia.

Research Products

• [Journal Article] Multiple therapeutic effects of progranulin on experimental acute ischemic stroke. (2015)
  • Author(s): Kanazawa K, Kawamura K, Takahashi T, Miura M, Tanaka Y, Koyama M, Toriyabe M, Igarashi H, Nakada T, Nishihara M, Nishizawa M, Shimohata T
  • Journal Title: Brain Volume: 79 Issue: 7 Pages: 1-17
  • DOI: 10.1093/brain/awv079
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Effects of Alda-1, an aldehyde dehydrogenase-2 agonist, on hypoglycemic neuronal death (2015)
  • Author(s): Ikeda T, Takahashi T, Tsujita M, Kanazawa M, Toriyabe M, Koyama M, Itoh K, Nakada T, Nishizawa M, Shimohata T
  • Journal Title: PLoS One Volume: 10
  • Peer Reviewed
• [Journal Article] Effects of angiopoietin-1 on hemorrhagic transformation and cerebral edema after tissue plasminogen activator treatment for ischemic stroke in rats. (2014)
  • Author(s): Kawamura K, Takahashi T, Kanazawa M, Igarashi H, Nakada T, Nishizawa M, Shimohata T.
  • Journal Title: PLoS One Volume: 9
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] プログラニュリンは実験虚血モデルにおいて，多面的治療効果をもつ (2015)
  • Author(s): 金澤 雅人, 川村 邦雄, 高橋 哲哉, 三浦 南, 田中 良法, 小山 美咲, 鳥谷部 真史, 五十嵐 博中, 中田 力, 西原 眞杉, 西澤 正豊, 下畑 享良
  • Organizer: 日本脳卒中学会総会
  • Place of Presentation: 広島, リーガロイヤルホテル広島
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Multiple therapeutic effects of progranulin on experimental acute ischemic stroke (2015)
  • Author(s): Masato Kanazawa, Kunio Kawamura, Tetsuya Takahashi, Minami Miura, Yoshinori Tanaka, Misaki Koyama, Masafumi Toriyabe, Hironaka Igarashi, Tsutomu Nakada, Masugi Nishihara, Masatoyo Nishizawa, Takayoshi Shimohata
  • Organizer: International Stroke Conference of American Stroke Association
  • Place of Presentation: Nashville, USA
  • Year and Date: 2015-02-12 – 2015-02-14
• [Presentation] プログラニュリンは神経細胞保護効果・抗炎症作用をもつ (2014)
  • Author(s): 三浦 南, 金澤 雅人, 川村 邦雄, 高橋 哲哉, 田中 良法, 小山 美咲, 鳥谷部 真史, 五十嵐 博中, 中田 力, 西原 眞杉, 西澤 正豊, 下畑 享良
  • Organizer: 日本脳循環代謝学会総会
  • Place of Presentation: 岡山, 岡山コンベンションセンター
  • Year and Date: 2014-11-20 – 2014-11-22
• [Presentation] 脳虚血におけるヘパラナーゼによる ヘパラン硫酸プロテオグリカンの修飾 (2014)
  • Author(s): 金澤 雅人, Yu-Huan Gu, 長田 高志, Brian T. Hawkins, 福田 俊一, 中島 元夫, 下畑 享良, 西澤 正豊, Gregory J. del Zoppo
  • Organizer: 日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 大阪, 千里ライフサイエンスセンター
  • Year and Date: 2014-08-08 – 2014-08-09
• [Presentation] アンギオポエチン１による血栓溶解療法に伴う脳出血合併症の予防効果 (2014)
  • Author(s): 金澤 雅人, 川村 邦雄, 高橋 哲哉, 五十嵐 博中, 中田 力, 西澤 正豊, 下畑 享良
  • Organizer: 日本神経学会学術大会
  • Place of Presentation: 福岡, 福岡国際会議場
  • Year and Date: 2014-05-21 – 2014-05-23
• [Presentation] Effects of angiopoietin-1 on hemorrhagic transformation and cerebral edema after tissue plasminogen activator treatment for ischemic stroke (2014)
  • Author(s): Masato Kanazawa, Kunio Kawamura, Tetsuya Takahashi, Hironaka Igarashi, Tsutomu Nakada, Masatoyo Nishizawa, Takayoshi Shimohata
  • Organizer: Annual Meeting of American Academy of Neurology
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2014-04-28 – 2014-05-03
• [Presentation] 脳虚血におけるヘパラナーゼによるヘパラン硫酸プロテオグリカンの修飾
  • Author(s): 金澤雅人
  • Organizer: 日本脳循環代謝学会
  • Place of Presentation: 札幌
• [Presentation] 脳虚血早期のヘパラナーゼによるヘパラン硫酸の脱糖鎖反応
  • Author(s): 金澤雅人
  • Organizer: 日本脳卒中学会
  • Place of Presentation: 大阪