title: Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism.
abstract: OBJECTIVE
  We tested the hypothesis that endothelial progenitor cell (EPC)-mediated functional recovery after stroke may be associated with the endothelial nitric oxide synthase (eNOS)/brain-derived neurotrophic factor (BDNF) signaling pathway.
  
  
  METHODS
  Mice were infused with either EPCs or saline after being subjected to middle cerebral artery occlusion. The EPC-treated mice also received intravenous injections of either Nω-nitro-l-arginine methyl ester (L-NAME, the NOS inhibitor) or saline.
  
  
  RESULTS
  The activation of eNOS and the expression of BDNF were significantly increased in ischemic brain of the EPC-treated mice, along with increased angiogenesis and neurogenesis. On diffusion tensor imaging (DTI), significant increases in fractional anisotropy and fiber count were observed in white matter, indicating axonal growth stimulated by EPCs. However, the EPC-treated mice that were received an L-NAME injection failed to exhibit the observed increases in angiogenesis, neurogenesis, and axonal growth. In addition, the neurons cocultured with EPCs in vitro exhibited the increased expression of BDNF and decreased apoptosis after oxygen-glucose deprivation compared with the control group. This EPC-induced protective effect was virtually absent in the L-NAME treatment group.
  
  
  CONCLUSIONS
  The eNOS/BDNF pathway may be involved in the EPC-mediated functional recovery of stroke mice. DTI is feasible for dynamically tracking the orientation of axonal projections after EPC treatment.
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Bai
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Xin-Gui
authors.initials: XG
authors.lastname: Peng
authors.affiliation: Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Li-Shan
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Zi-Hui
authors.initials: ZH
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Yuan-Cheng
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Chun-Qiang
authors.initials: CQ
authors.lastname: Lu
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Pei-Cheng
authors.initials: PC
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Sheng-Hong
authors.initials: SH
authors.lastname: Ju
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D066026:Endothelial Progenitor Cells / Q000502:physiology* / Q000637:transplantation*; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000601:surgery*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000628:therapy; D009422:Nervous System Diseases / Q000209:etiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; D052250:Nitric Oxide Synthase Type III; D010751:Phosphopyruvate Hydratase; D019331:NG-Nitroarginine Methyl Ester
keywords: Brain-derived neurotrophic factor; Diffusion tensor imaging; Endothelial nitric oxide synthase; Endothelial progenitor cells; Ischemic stroke