New treatment method of cerebral infarction with infiltrating cells

2013 Fiscal Year Final Research Report

• Project/Area Number: 23592092
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Ehime University
• Principal Investigator: KUMON YOSHIAKI 愛媛大学, 医学(系)研究科(研究院), 准教授 (80127894)
• Co-Investigator(Kenkyū-buntansha): WATANABE Hideaki 愛媛大学, 大学院医学系研究科, 講師 (30322275)
• Project Period (FY): 2011 – 2013
• Keywords: 脳血管障害学

Research Abstract

BINCs (Brain Iba1+/NG2+ Cells) accumulate in the ischemic core (IC), and may play neuroprotectively. The chemokine-based mechanisms underlying the invasion of BINCs were investigated.
We found isolated BINCs expressed mRNA encoding CCR2 and CX3CR1 at high levels. Cultured astrocytes expressed mRNA encoding their ligands, MCP-1 and fractalkine (FK). Recombinant MCP-1 and/or FK, as well as astrocytes, induced the migration of BINCs in vitro. The mRNA for MCP-1, FK, CCR2, and CX3CR1 was expressed in the IC during the acute phase. Immunohistochemical studies revealed vascular endothelial cells and astrocytic endfeet expressed MCP-1 and FK. CCR2+/Iba1+ monocytes attached to the inside of vascular wall at 1 day post-ischemia (dpi), and there were CCR2+/CX3CR1+ macrophage-like cells in the parenchyma of the IC at 2 dpi, which may be progenitors for BINCs. These results suggest CCR2+ monocytes are first attracted to the IC by MCP-1+ endothelial cells and migrate toward FK+ astrocytic endfeet.

Research Products

• [Journal Article] Activated microglia in a rat stroke model express NG2 proteoglycan in peri-infarct tissue through the involvement of TGF-β1 (2014)
  • Author(s): SUGIMOTO Kana, NISHIOKA Ryutaro, IKEDA Airi, MISE Ayano, TAKAHASHI Hisaaki, YANO Hajime, KUMON Yoshiaki, OHNISHI Takanori, TANAKA Junya
  • Journal Title: Glia Volume: 62 Pages: 185-198
  • DOI: 10.1002/glia.22598
  • Peer Reviewed
• [Journal Article] WATANABE Hideaki, KUMON Yoshiaki, OHNISHI Takanori : Expression of MCP-1 and Fractalkine on Endotherial Cells and Astrocytes May Contribute to the invasion and migration of brain macrophages in ischemic rat brain lesions (2013)
  • Author(s): TEI Nari, TANAKA Junya, SUGIMOTO Kana, NISHIHARA Tasuku, NISHIOKA Ryutaro, TAKAHASHI Hisaaki, YANO Hajime, MATSUMOTO Shirabe, OHUE Shiro
  • Journal Title: Journal of Neuroscience Research Volume: 91 Pages: 681-693
  • DOI: 10.1002/jnr.23202.Epub2013Feb12
  • Peer Reviewed
• [Journal Article] Subcutaneous injection containing IL-3 and GM-CSF ameliorates stab wound-induced brain injury in rats (2011)
  • Author(s): NISHIHARA Tasuku, OCHI Michihisa, SUGIMOTO Kana, TAKAHASHI Hisaaki, YANO Hajime, KUMON Yoshiaki, OHNOSHI Takanori, TANAKA Junya
  • Journal Title: Experimental Neurology Volume: 229巻 Pages: 507-516
  • DOI: 10.1016/j.expneurol.2011.04.006
  • Peer Reviewed
• [Presentation] 脳梗塞巣に集結するマクロファージ様細胞におけるCD200 / CD200Rの機能 (2014)
  • Author(s): 松本調、渡邉英昭、久門良明、大西丘倫、田中潤也
  • Organizer: 第39回日本脳卒中学会総会
  • Place of Presentation: 大阪市
  • Year and Date: 20140313-15
• [Presentation] BINCs (Brain Iba1+/NG2+ Cells)の脳梗塞巣への侵入機序の検討 (2012)
  • Author(s): 鄭菜里、渡邉英昭、久門良明、大西丘倫、田中潤也
  • Organizer: 第71回日本脳神経外科学会学術総会
  • Place of Presentation: 大阪市
  • Year and Date: 20121017-19
• [Presentation] BINCs (Brain Iba1+/NG2+ Cells)の脳梗塞巣への侵入機序の検討 (2011)
  • Author(s): 鄭菜里、渡邉英昭、久門良明、大西丘倫、田中潤也
  • Organizer: 第36回日本脳卒中学会総会
  • Place of Presentation: 京都市
  • Year and Date: 20110730-0801