Microglia and blood-derived macrophage in brain after stroke

Research Project

Project/Area Number	26350591
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Rehabilitation science/Welfare engineering
Research Institution	Nippon Medical School
Principal Investigator	NISHIYAMA Yasuhiro 日本医科大学, 医学部, 准教授 (20350077)
Project Period (FY)	2014-04-01 – 2018-03-31
Project Status	Completed (Fiscal Year 2017)
Budget Amount *help	¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000) Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000) Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000) Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords	ミクログリア / マクロファージ / 脳梗塞 / マウス / 単球 / 脳虚血マウスモデル / 炎症性サイトカイン / 脳虚血モデル
Outline of Final Research Achievements	Microglia and Mφ(Mφ)play significant roles in infection control, tissue repair, and sterile inflammation. However, some mechanisms are still unknown. We first showed the in vivo time course of types of microglia and Mφin the brain after stroke, Ly6Chi Mφinfiltrated and peaked by d3, followed by increased numbers of Ly6Clo Mφ by d5. But, microglia in the brain didn’t show a significant change the number of them in the time course. Also, from the molecular level, the dominant Mφpopulation at d3 after stroke, Ly6Chi Mφ, expressed more Arg-1, VEGF-a and IGF-2g and less IGF-1, CCL-3, TNF than the Ly6Clo Mφ. This means that Ly6Chi Mφ show more of M2-like pattern, whereas Ly6Clo Mφshow more of M1-like pattern. However, we didn’t show significant patterns in microglia. It is also very interesting to find that these Mφ but microglia turned into one another over time, suggesting more of a continuum of the functional phenotype, rather than classifying them in a strict binary fashion.