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Therapeutic effect of placenta-derived mesenchymal stem cells on hypoxic-ischemic brain damage in rats

World Journal of Pediatrics volume 11, pages 74–82 (2015)Cite this article

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, 5×105 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.

Conclusion

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.

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Affiliations

  1. Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, 250012, China

    Hui-Fang Ding, Dong Li & Xiu-Li Ju

  2. Department of Pediatrics, Shengli Oil Field Central Hospital, Dongying, 257034, China

    Hong-Fang Ding, Hui-Fang Ding, Xin-Hao Yi, Xin-Yi Gao & Wei-Wei Mou

  3. Department of Neurology, Qingdao Municipal Hospital, Qingdao, 266000, China

    Hui Zhang

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  1. Hong-Fang Ding
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Ding, HF., Zhang, H., Ding, HF. et al. Therapeutic effect of placenta-derived mesenchymal stem cells on hypoxic-ischemic brain damage in rats. World J Pediatr 11, 74–82 (2015). https://doi.org/10.1007/s12519-014-0531-8

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  • DOI: https://doi.org/10.1007/s12519-014-0531-8

Key words

  • hypoxia-ischemia
  • mesenchymal stem cells
  • neonatal rat
  • oxidative stress