title: Therapeutic effect of placenta-derived mesenchymal stem cells on hypoxic-ischemic brain damage in rats.
abstract: BACKGROUND
  Oxidative stress is involved in the development of hypoxic-ischemic brain damage (HIBD). In this study, we investigated the therapeutic effects of placenta-derived mesenchymal stem cells (PD-MSCs) and explored the NF-E2-related factor-2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway in treating HIBD.
  
  
  METHODS
  P7 rats were subjected to hypoxic-ischemic brain injury and randomly divided into four groups (control, HIBD, HIBD+PD-MSCs, and HIBD+fibroblasts). Forty-eight hours after the induction of HIBD, 5×10(5) of PD-MSCs were injected into cerebral tissue in the HIBD+PD-MSCs group, while the same dose of fibroblasts were injected in the HIBD+fibroblasts group. Morris Water Maze, gross and pathological changes were tested at P28. The level of malondialdehyde (MDA) was detected in rats' hippocampus. RT-PCR and western blot analysis were used to evaluate the changes of Nrf2/HO-1.
  
  
  RESULTS
  The HIBD group showed significantly longer escape latency and a lower frequency of original platform crossing in the Morris Water Maze compared with the control group. Rats receiving PD-MSCs showed significant improvement of HIBD. The pathological changes were evident after HIBD, but ameliorated in the PD-MSCs group. Compared with the control group, HO-1 and Nrf2 were up-regulated at gene and protein levels in the HI brain, beginning at 6 hours and peaking at 48 hours (P<0.05). The expression of HO-1 and Nrf2 in the PD-MSCs treatment group was more pronounced than in the HIBD group (P<0.01). PD-MSCs also decreased MDA production in the brain tissue.
  
  
  CONCLUSIONS
  These results demonstrate that PD-MSCs have neuroprotective effect during the treatment of HIBD and that the mechanism may be partly due to alleviating oxidative stress.
authors.affiliation: Department of Pediatrics, Shengli Oil Field Central Hospital, Dongying, 257034, China.
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Ding
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Ding
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Xin-Hao
authors.initials: XH
authors.lastname: Yi
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Gao
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Mou
authors.forename: Xiu-Li
authors.initials: XL
authors.lastname: Ju
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology / Q000628:therapy*; D008315:Malondialdehyde / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D051381:Rats; D015398:Signal Transduction / Q000502:physiology; D014162:Transfection
chemical_list: D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D008315:Malondialdehyde; D051547:Heme Oxygenase-1