Bone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism

• Published in: CNS neuroscience & therapeutics Vol. 21; no. 11; pp. 877 - 886
• Main Authors: Bai, Ying‐Ying, Peng, Xin‐Gui, Wang, Li‐Shan, Li, Zi‐Hui, Wang, Yuan‐Cheng, Lu, Chun‐Qiang, Ding, Jie, Li, Pei‐Cheng, Zhao, Zhen, Ju, Sheng‐Hong
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.11.2015; John Wiley and Sons Inc
• Subjects: Angiogenesis; Animals; Bone Marrow Transplantation - methods; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Cells, Cultured; Coculture Techniques; Diffusion tensor imaging; Disease Models, Animal; Endothelial nitric oxide synthase; Endothelial progenitor cells; Endothelial Progenitor Cells - physiology; Endothelial Progenitor Cells - transplantation; Enzyme Inhibitors - therapeutic use; Glial Fibrillary Acidic Protein - metabolism; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - drug therapy; Infarction, Middle Cerebral Artery - surgery; Ischemic stroke; Male; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic - etiology; Neovascularization, Pathologic - therapy; Nervous System Diseases - etiology; Neurogenesis; Neurogenesis - drug effects; Neurogenesis - physiology; Neurons - drug effects; NG-Nitroarginine Methyl Ester - therapeutic use; Nitric oxide; Nitric Oxide Synthase Type III - metabolism; Original; Phosphopyruvate Hydratase - metabolism; Time Factors; Endothelial nitric oxide synthase; Brain-derived neurotrophic factor; Ischemic stroke; Endothelial progenitor cells; Diffusion tensor imaging
• ISSN: 1755-5930; 1755-5949
• DOI: 10.1111/cns.12447

Summary 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 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. 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.