title: Rat umbilical cord blood cells attenuate hypoxic-ischemic brain injury in neonatal rats.
abstract: Increasing evidence has suggested that human umbilical cord blood cells (hUCBC) have a favorable effect on hypoxic-ischemic (HI) brain injury. However, the efficacy of using hUCBCs to treat this injury has been variable and the underlying mechanism remains elusive. Here, we investigated its effectiveness using stereological analysis in an allogeneic system to examine whether intraperitoneal injection of cells derived from UCBCs of green fluorescent protein (GFP)-transgenic rats could ameliorate brain injury in neonatal rats. Three weeks after the HI event, the estimated residual brain volume was larger and motor function improved more in the cell-injected rats than in the control (PBS-treated) rats. The GFP-positive cells were hardly detectable in the brain (0.0057% of injected cells) 9 days after injection. Although 60% of GFP-positive cells in the brain were Iba1-positive, none of these were positive for NeuroD or DCX. While the number of proliferating cells increased in the hippocampus, that of activated microglia/macrophages decreased and a proportion of M2 microglia/macrophages increased in the ipsilateral hemisphere of cell-injected rats. These results suggest that intraperitoneal injection of cells derived from UCBCs could ameliorate HI injury, possibly through an endogenous response and not by supplying differentiated neurons derived from the injected stem cells.
authors.affiliation: Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kagiya-cho, Kasugai, Aichi, 480-0392, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kagiya-cho, Kasugai, Aichi, 480-0392, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mizutani
authors.affiliation: Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
authors.forename: Miharu
authors.initials: M
authors.lastname: Ito
authors.affiliation: Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Hirakawa
authors.affiliation: Department of Perinatology, Institute for Developmental Research, Aichi Human Service Center, 713-8 Kagiya-cho, Kasugai, Aichi, 480-0392, Japan.
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Higashi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D000089662:Doublecortin Protein; D005312:Fetal Blood / Q000637:transplantation*; D006624:Hippocampus / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000628:therapy*; D007249:Inflammation / Q000150:complications / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D009043:Motor Activity; D009474:Neurons / Q000502:physiology; D051381:Rats; D055647:Rats, Transgenic; D014184:Transplantation, Homologous