title: Administration of umbilical cord blood cells transiently decreased hypoxic-ischemic brain injury in neonatal rats.
abstract: This study aimed to investigate whether the administration of mononuclear cells derived from human umbilical cord blood cells (UCBCs) could ameliorate hypoxic-ischemic brain injury in a neonatal rat model. The left carotid arteries of 7-day-old rats were ligated, and the rats were then exposed to 8% oxygen for 60 min. Mononuclear cells derived from UCBCs using the Ficoll-Hypaque technique were injected intraperitoneally 6 h after the insult (1.0 × 10(7) cells). Twenty-four hours after the insult, the number of cells positive for the oxidative stress markers 4-hydroxy-2-nonenal and nitrotyrosine, in the dentate gyrus of the hippocampus in the UCBC-treated group, decreased by 36 and 42%, respectively, compared with those in the control group. In addition, the number of cells positive for the apoptosis markers active caspase-3 and apoptosis-inducing factor decreased by 53 and 58%, respectively. The number of activated microglia (ED1-positive cells) was 51% lower in the UCBC group compared with the control group. In a gait analysis performed 2 weeks after the insult, there were no significant differences among the sham-operated, control and UCBC groups. An active avoidance test using a shuttle box the following week also revealed no significant differences among the groups. Neither the volumes of the hippocampi, corpus callosum and cortices nor the numbers of neurons in the hippocampus were different between the UCBC and control groups. In summary, a single intraperitoneal injection of UCBC-derived mononuclear cells 6 h after an ischemic insult was associated with a transient reduction in numbers of apoptosis and oxidative stress marker-positive cells, but it did not induce long-term morphological or functional protection. Repeated administration or a combination treatment may be required to achieve sustained protection.
authors.affiliation: Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hattori
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.forename: Taiki
authors.initials: T
authors.lastname: Kondo
authors.forename: Yuko
authors.initials: Y
authors.lastname: Ichinohashi
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Michiro
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kotani
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hirata
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirakawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Suzuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tsuji
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hayakawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology*; D004195:Disease Models, Animal; D005312:Fetal Blood / Q000637:transplantation*; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D007274:Injections, Intraperitoneal; D007963:Leukocytes, Mononuclear / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar