Research on the Neurorestorative Effects of Human Neural Stem Cell Transplantation in Rats with Hypoxic-Ischemic Encephalopathy
Objective To explore transplanted human neural stem cells(hNSCs)for the treatment of moderate and severe hypoxic-ischemic encephalopathy(HIE)in neonatal rats and its mechanisms of neuroprotection during the sequela peri-od.Methods Eighty 7-day-old male SD rats were randomly selected.Among them,55 rats were randomly selected to make HIE model by Rice-Vannucci method.After modeling for 24 h,the surviving rats with moderate and severe injury were screened out by Longa score and randomly divided into HIE+PBS group(PBS group,n=23)and HIE+hNSCs group(NSC group,n=23).Twenty-three rats were randomly selected from the remaining 25 rats as Sham operation group(Sham group,n=23).In Sham group,there was only the isolation of the right common carotid artery without dissection or hypoxia.Simultaneous drug adminis-tration was conducted to suppress rejection reactions took place in all three groups.Three days after modeling,the PBS and NSC groups were administered with 5 μL of PBS solution or hNSCs suspension via right intraventricular transplantation,respective-ly.Ten days post-transplantation,15 rats from each group were randomly selected for an enzyme-linked immunosorbent assay(ELISA)to measure the levels of vascular endothelial growth factor(VEGF)and brain-derived neurotrophic factor(BDNF),im-munofluorescent staining was used to observe the distribution of the two factors.Twelve weeks after transplantation,immuno-fluorescent staining was used to observe the migration and differentiation of hNSCs in the brains of the NSC group rats,and the remaining 8 rats from each group underwent a water maze test to assess neural function.Results Ten days after transplanta-tion,the levels of VEGF and BDNF were the highest in the NSC group,followed by the PBS group and the Sham group,and the levels of both factors were higher in the NSC group than in the Sham group(all P＜0.05).Twelve weeks after transplantation,hNSCs migrated to both hemispheres of HIE rats,mainly to the right side,and the mature neuron differentiation rate was about 30％.Twelve weeks after transplantation,the latency of the PBS group was longer than that of the Sham and NSC groups in the water maze test,and the times of platform crossing of the PBS group were shorter than that of the Sham and NSC groups(all P＜0.05),but there was no significant difference between the Sham and NSC groups(P＞0.05).Conclusion Ventricular trans-plantation of hNSCs can enhance the paracrine effect of VEGF and BDNF in the brain of HIE rats and the substitution effect of migration and differentiation into neurons,thus promoting the repairment of nerve injury in the sequela of HIE rats and provi-ding new ideas for the treatment of HIE.
neonatal hypoxic ischemic encephalopathybrain-derived neurotrophic factorcell migrationcell differ-entiationMorris water maze
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