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

Background:Oxidative stress is involved in the development of hypoxic-ischemic brain damage(HIBD).In this study,we investigated the therapeutic efcts of placenta-derived mesenchymal stem cells(PD-MSCs)and explored the N F-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+fbroblasts).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 fibroblas ts 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 M laze 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 HBD 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.