title: Transplantation of bone marrow-derived endothelial progenitor cells             attenuates cerebral ischemia and reperfusion injury by inhibiting neuronal apoptosis,             oxidative stress and nuclear factor-κB expression.
abstract: The aim of the present study was to investigate the neuroprotective effects             of bone marrow-derived endothelial progenitor cell (EPC) transplantation against             cerebral ischemia/reperfusion (I/R) injury in rats and to delineate the possible             underlying mechanisms. Cerebral I/R injury was established by 2 h of middle cerebral             artery occlusion (MCAO) followed by reperfusion for 24 h. EPCs were isolated from             bone marrow of the donor rats, grown in conditioned medium, and characterized             by flow cytometry analysis of several surface markers. Labeled EPCs (106 cells)             were infused into rats at the onset of reperfusion and 12 h after reperfusion             via the tail vein. Infarct volume was assessed at 24 h after reperfusion by using             triphenyltetrazolium chloride (TTC) staining. The expression of cell apoptosis-related             proteins including Bcl-2 and Bax was determined by western blot analysis, and             the activity of caspase-3 was also measured. We evaluated the activities of some             antioxidative enzymes, such as superoxide dismutase (SOD), glutathione peroxidase             (GSH-PX), the non-enzymatic scavenger glutathione (GSH) and detected the content             of malondialdehyde (MDA) in the ischemic penumbra. Moreover, the expression of             nuclear factor-κB (NF-κB) in the ischemic regions of rats was examined by immunohistochemical             staining and western blot analysis. The results showed that transplantation of             EPCs significantly reduced the cerebral infarct volume, decreased caspase-3 activity,             upregulated Bcl-2 expression, and downregulated the expression of Bax and NF-κB.             Furthermore, reduced levels of MDA, significantly elevated activities of SOD and             GSH as well as GSH-PX were also found in I/R rats transplanted with EPCs. Collectively,             our data demonstrated that transplantation of bone marrow-derived EPCs exerts             potent neuroprotective functions against cerebral I/R injury in rats, and the             protective effects may be associated with its antioxidative and anti-apoptotic             properties.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Qiu
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Shuhang
authors.initials: S
authors.lastname: Feng
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: He
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002544:Cerebral Infarction / Q000517:prevention & control*; D004195:Disease Models, Animal; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013234:Stem Cells / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013778:Tetrazolium Salts / Q000378:metabolism; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D016328:NF-kappa B; D013778:Tetrazolium Salts; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; C009591:triphenyltetrazolium; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C505410:Casp3 protein, rat; D053148:Caspase 3; D005978:Glutathione