umbilical cord blood mononuclear cell (UCBMC), hypoxic ischemic brain damage (HIBD), toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB), TLR4/NF-κB pathway, neonatal rats
Objective:This study aims to observe the effects of transplantation of umbilical cord blood mononuclear cells (UCBMCs) on the expression of interleukin (IL)-1β and explore the mechanism via the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway in hypoxic-ischemic neonatal rats.Methods:Seven-day-old Sprague-Dawley neonatal rats were randomly divided into Sham, hypoxic-ischemic brain damage (HIBD), and UCBMC groups. The HIBD model was prepared by Rice-Vannucci method, and UCBMC were transplanted 24 h after HIBD in the UCBMC group. At 7 days after transplantation, changes in neurons and the TLR4 protein were examined by neuronal nuclei (NeuN)/TLR4 immunofluorescence staining. The expression of pNF-κB and IL-1β proteins was detected by immunohistochemical staining and enzyme linked immunosorbent assay (ELISA).Results:The percentage of NeuN+DAPI+ cells in the injured cortex in the UCBMC group was significantly higher than that in the HIBD group and lower than that in the Sham group (P < 0.05). The number of NeuN+TLR4+DAPI+cells in the UCBMC group was significantly lower than that in the HIBD group (P < 0.05) but higher than that in the Sham group (P < 0.05). More pNF-κB+ cells were observed in the HIBD group than in Sham and UCBMC groups (P < 0.05), and more pNF-κB+ cells were observed in the UCBMC group than in the Sham group (P < 0.05). ELISA results showed that the IL-1β expression in the injured cerebral cortex in the UCMBC group was significantly lower than that in the HIBD group but remained higher than that in the Sham group (P < 0.05).Conclusions:UCBMC transplantation could inhibit the IL-1β protein expression in the injured cortex, thereby alleviating HIBD in neonatal rats. The underlying mechanism might be associated with the down- regulation of TLR4 and pNF-κB proteins.
Tsinghua University Press
Meng-Bei Zhang, Chao-Chao Song, Guang-Zu Li et al. Transplantation of umbilical cord blood mononuclear cells attenuates the expression of IL-1β via the TLR4/NF-κB pathway in hypoxic-ischemic neonatal rats. Journal of Neurorestoratology 2020, 8(2): 122-130.