Abstract：
Activin A (Act A) has been reported to promote oligodendrocyte progenitor cell (OPC) differentiation in vitro and improve neurological outcomes in adult mice. However, the roles and mechanisms of action of Act A in preterm brain injury are unknown. In the present study, P5 rats were subjected to hypoxia‑ischemia to establish a neonatal white matter injury (WMI) model and Act A was injected via the lateral ventricle. Pathological characteristics, OPC differentiation, myelination, and neurological performance were analyzed. Further, the involvement of the Noggin/BMP4/Id2 signaling pathway in the roles of Act A in WMI was explored. Act A attenuated pathological damage, promoted OPC differentiation, enhanced myelin sheath and myelinated axon formation, and improved neurological performance of WMI rats. Moreover, Act A enhanced noggin expression, which, in turn, inhibited the expression of bone morphogenetic protein 4 (BMP4) and inhibitor of DNA binding 2 (Id2). Furthermore, upregulation of Id2 completely abolished the rescue effects of Act A in WMI rats. In conclusion, the present findings suggested that Act A rescues preterm brain injury via targeting a novel Noggin/BMP4/Id2 signaling pathway.
摘要：
已报道激活素A(ActA)在体外促进少突胶质祖细胞(OPC)分化并改善成年小鼠的神经学结果。然而,A行为在早产脑损伤中的作用和作用机制尚不清楚。在本研究中,对P5大鼠进行缺氧缺血以建立新生儿白质损伤（WMI）模型，并通过侧脑室注射ActA。病理特征,OPC区分,髓鞘形成,并对神经系统表现进行了分析。Further,本研究探讨了Noggin/BMP4/Id2信号通路参与ActA在WMI中的作用。A行动减轻了病理损伤，促进OPC差异化，增强髓鞘和有髓鞘的轴突形成，改善WMI大鼠的神经功能。此外，行动增强了noggin表达，which,反过来,抑制骨形态发生蛋白4（BMP4）和DNA结合抑制剂2（Id2）的表达。此外，Id2的上调完全消除了A法案在WMI大鼠中的挽救作用。总之,本研究结果表明,ActA通过靶向一种新的Noggin/BMP4/Id2信号通路来挽救早产脑损伤.
