title: Transplantation of human umbilical cord blood cells mediated beneficial effects on apoptosis, angiogenesis and neuronal survival after hypoxic-ischemic brain injury in rats.
abstract: Transplantation of human umbilical cord blood (hucb) cells in a model of hypoxic-ischemic brain injury led to the amelioration of lesion-impaired neurological and motor functions. However, the mechanisms by which transplanted cells mediate functional recovery after brain injury are largely unknown. In this study, the effects of hucb cell transplantation were investigated in this experimental paradigm at the cellular and molecular level. As the pathological cascade in hypoxic-ischemic brain injury includes inflammation, reduced blood flow, and neuronal cell death, we analyzed the effects of peripherally administered hucb cells on these detrimental processes, investigating the expression of characteristic marker proteins. Application of hucb cells after perinatal hypoxic-ischemic brain injury correlated with an increased expression of the proteins Tie-2 and occludin, which are associated with angiogenesis. Lesion-induced apoptosis, determined by expression of cleaved caspase-3, decreased, whereas the number of vital neurons, identified by counting of NeuN-positive cells, increased. In addition, we observed an increase in the expression of neurotrophic and pro-angiogenic growth factors, namely BDNF and VEGF, in the lesioned brain upon hucb cell transplantation. The release of neurotrophic factors mediated by transplanted hucb cells might cause a lower number of neurons to undergo apoptosis and result in a higher number of living neurons. In parallel, the increase of VEGF might cause growth of blood vessels. Thus, hucb transplantation might contribute to functional recovery after brain injury mediated by systemic or local effects.
authors.affiliation: Department of Functional Proteomics, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Rosenkranz
authors.forename: Sandra
authors.initials: S
authors.lastname: Kumbruch
authors.forename: Matthias
authors.initials: M
authors.lastname: Tenbusch
authors.forename: Katrin
authors.initials: K
authors.lastname: Marcus
authors.forename: Katrin
authors.initials: K
authors.lastname: Marschner
authors.forename: Rolf
authors.initials: R
authors.lastname: Dermietzel
authors.forename: Carola
authors.initials: C
authors.lastname: Meier
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D036101:Cord Blood Stem Cell Transplantation; D005312:Fetal Blood / Q000166:cytology* / Q000637:transplantation*; D005786:Gene Expression Regulation; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000628:therapy*; D008565:Membrane Proteins / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D062793:Occludin; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D042787:Receptor, TIE-2 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; C568987:Ocln protein, rat; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2; D053148:Caspase 3