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.
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.
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