Open AccessBone Marrow Endothelial Progenitor Cell Transplantation After Ischemic Stroke: An Investigation Into Its Possible Mechanism
Author(s) -
Bai YingYing,
Peng XinGui,
Wang LiShan,
Li ZiHui,
Wang YuanCheng,
Lu ChunQiang,
Ding Jie,
Li PeiCheng,
Zhao Zhen,
Ju ShengHong
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12447
Subject(s) - enos , neurogenesis , progenitor cell , angiogenesis , endothelial progenitor cell , medicine , transplantation , neurotrophic factors , fractional anisotropy , endocrinology , nitric oxide , nitric oxide synthase , chemistry , neuroscience , white matter , stem cell , biology , microbiology and biotechnology , receptor , radiology , magnetic resonance imaging
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 EPC s 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 EPC s. 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 EPC s 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.