BackgroundActivin A (Act A) has been revealed to enhance the differentiation of oligodendrocyte progenitor cells (OPCs) in vitro. Here we aim to elucidate its roles and mechanisms in a rat model of white matter injury (WMI). MethodsAct A was injected into the lateral ventricle of a hypoxia-ischemia induced WMI rat model. Hematoxylin & eosin staining was used to detect pathological changes. Immunofluorescence staining was used to assess OPC proliferation, migration, apoptosis, and

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... . Myelin sheath and axon formation were detected via immunofluorescence staining, Western blotting, and electron microscopy. Behavioral assessment of rats was performed with the Morris water maze test. ResultsAct A attenuated the pathological damages, enhanced the formation of myelin sheath and myelinated axons and improved the behavior of WMI rats by promoting OPC proliferation and differentiation. However, Act A showed no significant effects on OPC migration or apoptosis. Interestingly, we found that Act A could enhance 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 protective effects of Act A in WMI. ConclusionsAct A improves WMI in neonatal rats via Noggin/BMP4/Id2 signalling.