Search

Background: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation. Methods: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation. Results: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation. Conclusions: A2B5+OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway.

Interleukin 10 (IL-10) is a synthetic inhibitor of human cytokines with immunomodulatory and anti-inflammatory effects. This study was designed to investigate the expression variation of IL-10 in the multiple sites including cortex, hippocampus, and lung tissues of neonatal hypoxic-ischemic (HI) rats and explore the crucial role of IL-10 in alleviating HI brain damage. In this study, neonatal Sprague-Dawley rats were subjected to the right common carotid artery ligation, followed by 2 h of hypoxia. The expression of IL-10 in the cortex, hippocampus, and lung tissues was measured with immunohistochemistry, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot (WB). Immunofluorescence double staining was performed to observe the localization of IL-10 in neurons and astrocytes. Moreover, not-targeting and targeting IL-10 siRNA lentivirus vectors were injected into the rats of the negative control (NC) and IL-10 group, respectively, and the mRNA levels of B-cell lymphoma 2 (Bcl-2) and endoplasmic reticulum protein 29 (ERp29) were detected by RT-qPCR following IL-10 silence. The results demonstrated that the IL-10 expression was markedly increased after HI and IL-10 were colocalized with neurons and astrocytes which were badly injured by HI insult. In addition, Bcl-2 and ERp29 were remarkably decreased following IL-10 mRNA interference compared with the NC group. Our findings revealed that IL-10 exerted its antiapoptotic and neuroprotective effects by regulating the expression of Bcl-2 and ERp29, indicating that IL-10 may be a promising molecule target for HIE treatment. Refereed/Peer-reviewed

Background: The effect of interleukin-6 (IL-6) knockdown on hypoxia-ischemia (HI) of neonatal rat models was investigated to explore the underlying molecular regulation mechanism. Methods: To establish the HI model, we treated 7days postnatal Sprague-Dawley (SD) rats with the right carotid artery ligation and had them exposed to the environment of 8% oxygen and 92% nitrogen for 2 h, respectively. Then, the neurologic function and morphology changes were assessed. Subsequently, IL-6 siRNA lentivirus was injected into cerebral cortex motor area 2 days before HI; meanwhile, the interference efficiency was detected by quantitative real-time polymerase chain reaction (QRT-PCR) and Western blot. Immunofluorescence staining of Glial fibrillary acidic protein (GFAP), Hexaribonucleotide Binding Protein-3 (NeuN) and IL-6 were used to identify the location and interference effect of IL-6. In order to further research the underlying mechanisms, the expressions of downstream molecular including Bcl-2-associated X protein (BAX) and Casp3 were examined following IL-6 up-regulation by QRT-PCR.Results: It was found that both the growth of cortical neurons and the length of axon were promoted after IL-6 interference, and the cell apoptosis was decreased. In addition, the expression of BAX and Casp3 were closely associated with IL-6. Conclusions: The present findings confirmed that the decreased IL-6 improves the deficiencies in neurologic function and morphology induced by HI, and the potential mechanism may be closely related with the regulation of Casp3 and BAX.