PMID- 26384586 OWN - NLM STAT- MEDLINE DCOM- 20160722 LR - 20220316 IS - 1755-5949 (Electronic) IS - 1755-5930 (Print) IS - 1755-5930 (Linking) VI - 21 IP - 11 DP - 2015 Nov TI - Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism. PG - 877-86 LID - 10.1111/cns.12447 [doi] AB - AIMS: 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 Nomega-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. CONCLUSION: 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. CI - (c) 2015 John Wiley & Sons Ltd. FAU - Bai, Ying-Ying AU - Bai YY AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Peng, Xin-Gui AU - Peng XG AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Wang, Li-Shan AU - Wang LS AD - Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Li, Zi-Hui AU - Li ZH AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Wang, Yuan-Cheng AU - Wang YC AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Lu, Chun-Qiang AU - Lu CQ AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Ding, Jie AU - Ding J AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Li, Pei-Cheng AU - Li PC AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Zhao, Zhen AU - Zhao Z AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. FAU - Ju, Sheng-Hong AU - Ju SH AD - Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150919 PL - England TA - CNS Neurosci Ther JT - CNS neuroscience & therapeutics JID - 101473265 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Glial Fibrillary Acidic Protein) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 4.2.1.11 (Phosphopyruvate Hydratase) RN - V55S2QJN2X (NG-Nitroarginine Methyl Ester) SB - IM MH - Animals MH - Bone Marrow Transplantation/*methods MH - Brain-Derived Neurotrophic Factor/metabolism MH - Cells, Cultured MH - Coculture Techniques MH - Disease Models, Animal MH - Endothelial Progenitor Cells/*physiology/*transplantation MH - Enzyme Inhibitors/therapeutic use MH - Glial Fibrillary Acidic Protein/metabolism MH - Infarction, Middle Cerebral Artery/complications/drug therapy/*surgery MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NG-Nitroarginine Methyl Ester/therapeutic use MH - Neovascularization, Pathologic/etiology/therapy MH - Nervous System Diseases/etiology MH - Neurogenesis/drug effects/physiology MH - Neurons/drug effects MH - Nitric Oxide Synthase Type III/metabolism MH - Phosphopyruvate Hydratase/metabolism MH - Time Factors PMC - PMC6493116 OTO - NOTNLM OT - Brain-derived neurotrophic factor OT - Diffusion tensor imaging OT - Endothelial nitric oxide synthase OT - Endothelial progenitor cells OT - Ischemic stroke COIS- The authors declare no conflict of interest. EDAT- 2015/09/20 06:00 MHDA- 2016/07/23 06:00 PMCR- 2015/09/19 CRDT- 2015/09/20 06:00 PHST- 2014/10/17 00:00 [received] PHST- 2015/08/09 00:00 [revised] PHST- 2015/08/10 00:00 [accepted] PHST- 2015/09/20 06:00 [entrez] PHST- 2015/09/20 06:00 [pubmed] PHST- 2016/07/23 06:00 [medline] PHST- 2015/09/19 00:00 [pmc-release] AID - CNS12447 [pii] AID - 10.1111/cns.12447 [doi] PST - ppublish SO - CNS Neurosci Ther. 2015 Nov;21(11):877-86. doi: 10.1111/cns.12447. Epub 2015 Sep 19.