title: Metformin promotes focal angiogenesis and neurogenesis in mice following middle cerebral artery occlusion.
abstract: Current studies demonstrated that metformin is not only a hypoglycemic drug, but also a neuro-protective agent. However, the effect of metformin during ischemic brain injury is unclear. The aim of the present study is to explore the effect of metformin during ischemic brain injury. Adult male CD1 mice underwent 90min transient middle cerebral artery occlusion. Metformin (200mg/kg) was given at the time of reperfusion daily until sacrifice. Results showed that metformin treatment significantly reduced ischemia-induced brain atrophy volume compared to the control (p<0.05). Immunostaining results showed that the microvessel density in the peri-focal region of metformin treated mice was greatly increased compared to the control (p<0.05). Similarly, the numbers of BrdU+/DCX+ and nestin+ cells in the subventricular zone were increased in metformin treated mice compared to the control (p<0.05). Furthermore, we demonstrated that metformin treatment activated AMPK signaling pathway and promoted eNOS phosphorylation. Thus, we concluded that metformin promoted focal angiogenesis and neurogenesis and attenuated ischemia-induced brain injury in mice after middle cerebral artery occlusion, suggesting that metformin is a potential new drug for ischemic stroke therapy.
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
authors.forename: Yanqun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Tang
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yongting
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China; Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address: gyyang0626@gmail.com.
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
mesh_terms: D000818:Animals; D001284:Atrophy; D001921:Brain / Q000473:pathology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D000089662:Doublecortin Protein; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D020547:Lateral Ventricles / Q000473:pathology; D008026:Ligation; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D020768:Middle Cerebral Artery / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D055495:Neurogenesis / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects
chemical_list: C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D007004:Hypoglycemic Agents; D008687:Metformin; D052250:Nitric Oxide Synthase Type III; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: Angiogenesis; Ischemia; Metformin; Neurogenesis; Recovery