title: Restoration of tissue damage, and never activity after hypoxia-ischemia by implantation of peripheral blood mononuclear cells.
abstract: Hypoxia-ischemia (HI) encephalopathy is a frequent cause of disability and mortality with limited therapeutic options. Here, we collected peripheral blood mononuclear cells (PB-MNCs) from healthy donors and labeled them with CM-DiI before implanting these cells by tail-vein injection into rats at day 3 after hypoxia-ischemia (HI). For immune-suppression the animals received daily injections of cyclosporine throughout the experiment, commencing 24h before cell transplantation. Then we observed the PB-MNCs by fluorescent microscopy, examined motor function of rats by rotarod and cylinder tests, measured the lesion volume using image-pro plus software, and analyzed the apoptosis of neural cells in HI rats by tunnel assay. The results showed PB-MNCs could survive in the brain of hosts, migrate to the damage area and express neural marker. In addition, The HI rats that received PB-MNCs showed a reduction in motor function impairment, lesion volume and neural cell apoptosis. To better understand the mechanism of cell migration, PB-MNCs were also injected into normal rats via tail-vein. The expression of stromal cell-derived factor-1 (SDF-1) in the brain of normal and HI rats was measured by RT- PCR and western-blot, while the response of PB-MNCs in vitro to HI or normal brain extracts were measured by cell migration assay. Collectively these data suggest that the migration of PB-MNCs is directed to the damaged brain through an SDF-1-dependent pathway. Our results suggest that intravenous transplantation of PB-MNCs may be a feasible candidate for HI therapy.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Yu-xiao
authors.initials: YX
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Xiao-ming
authors.initials: XM
authors.lastname: Guo
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Jun-feng
authors.initials: JF
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Hai-tao
authors.initials: HT
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Ai-jun
authors.initials: AJ
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Shou-chun
authors.initials: SC
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Yuan-lin
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China. Electronic address: xuejh2009@yahoo.com.cn.
authors.forename: Jing-hui
authors.initials: JH
authors.lastname: Xue
authors.affiliation: Department of Cell Biology, Institute of Basic Medical Sciences, Beijing 100850, China. Electronic address: zhangyi_612@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, China. Electronic address: zhangzhiwen_301@yahoo.com.cn.
authors.forename: Zhi-wen
authors.initials: ZW
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000378:metabolism; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000637:transplantation*; D009043:Motor Activity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; D016179:Granulocyte Colony-Stimulating Factor
keywords: ANOVA; BM-MNCs; CB-MNCs; Cell transplantation; CsA; G-CSF; GFAP; HE; HI; Hypoxia–ischemia encephalopathy; Migration; PB-MNCs; Peripheral blood mononuclear cells; SD; SDF-1; Sprague-Dawley; Stromal cell-derived factor-1; TTC; analysis of variance; bone marrow mononuclear; cord blood mononuclear; cyclosporine A; glial fibrillary acidic protein; granulocyte colony-stimulating factor; hematoxylin and eosin; hypoxia–ischemia; peripheral blood mononuclear cells; stromal cell-derived factor-1; triphenyltetrazolium chloride