New treatment for cerebral infarction using infiltrating cells

2010 Fiscal Year Final Research Report

• Project/Area Number: 20591687
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cerebral neurosurgery
• Research Institution: Ehime University
• Principal Investigator: KUMON Yoshiaki Ehime University, 大学院・医学系研究科, 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): 2008 – 2010
• Keywords: 脳梗塞 / 浸潤細胞 / 神経栄養因子 / 治療

Research Abstract

We found that macrophage-like cells accumulate in the ischemic core of a rat brain whose right middle cerebral artery was transiently occluded for 90 minutes. Many of these cells expressed Iba1, a marker of macrophages/microglias, as well as NG2 chondroitin sulfate proteoglycan (NG2), which has been recognized as a marker of oligodendrocyte progenitor cells. Such macrophage-like cells were termed BINCs (brain Iba1+/NG2+cells). BINCs were highly proliferative and their number peaked at 7 days post-reperfusion. Taken the various function of NG2, BINCs may be involved in not only phagocytosis of degenerated cells but also the healing and regeneration of lesion cores. 5-Fluorouracil (5FU) injection at 2 days post reperfusion markedly reduced the number of BINCs at 7 days post reperfusion, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Bone marrow-derived BINCs play a benefical role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors.

Research Products

• [Journal Article] Iba+/NG2+ macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain. (2010)
  • Author(s): Smirkin A, Matsumoto H, Takahashi H, Inoue A, Tagawa M, Ohue S, Watanabe H, Yano H, Kumon Y, Ohnishi T, Tanaka J
  • Journal Title: Journal of Cerebral Blood Flow and Metabolism 30 Pages: 603-615
  • Peer Reviewed
• [Journal Article] Vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay for platelet response to cilostazol. (2010)
  • Author(s): Yamanouchi J, Hato T, Niiya T, Nakagawa K, Kumon Y, Fujiwara H, Yakushijin Y, Yasukawa M
  • Journal Title: Platelets, Epub
  • Peer Reviewed
• [Journal Article] Accumulation of macrophage-like cells expressing NG2 proteoglycan and Ibal in ischemic core of rat brain after transient middle cerebral artery occlusion. (2008)
  • Author(s): Matsumoto H, Kumon Y, Watanabe H, Ohnishi T, Shudou M, Chuai M, Imai Y, Takahashi H, Tanaka J
  • Journal Title: Journal of Cerebral Blood Flow and Metabolism 28 Pages: 149-163
  • Peer Reviewed
• [Journal Article] Postoperative temporary neurological deficits in adults with moyamoya disease. (2008)
  • Author(s): Ohue S, Kumon Y, Kohno K, Watanabe H, Iwata S, Ohnishi T
  • Journal Title: Surgical Neurology 69 Pages: 281-287
  • Peer Reviewed
• [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
  • Place of Presentation: 東京
  • Year and Date: 2011-03-26
• [Presentation] ラット虚血脳におけるケモカイン;フラクタルカインとMCP-1 (2010)
  • Author(s): 鄭菜里、渡邉英昭、久門良明、大西丘倫、田中潤也
  • Organizer: 第33回日本神経科学大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-09-02
• [Remarks] ホームページ等 無し