HBO Promotes the Differentiation of Neural Stem Cells via InteractionsBetween the Wnt3/β-Catenin and BMP2 Signaling Pathways

摘要

Hyperbaric oxygen (HBO) therapy may promote neurological recovery from hypoxic-ischemicencephalopathy (HIE). However, the therapeutic effects of HBO and its associatedmechanisms remain unknown. The canonical Wnt/β-catenin signaling pathways and bonemorphogenetic protein (BMP) play important roles in mammalian nervous system development.The present study examined whether HBO stimulates the differentiation of neural stem cells(NSCs) and its effect on Wnt3/β-catenin and BMP2 signaling pathways. We showed HBOtreatment (2 ATA, 60 min) promoted differentiation of NSCs into neurons andoligodendrocytes in vitro. In addition, rat hypoxic-ischemic brain damage (HIBD) tissueextracts also promoted the differentiation of NSCs into neurons and oligodendrocytes, withthe advantage of reducing the number of astrocytes. These effects were most pronouncedwhen these two were combined together. In addition, the expression of Wnt3a, BMP2, andβ-catenin nuclear proteins were increased after HBO treatment. However, blockade ofWnt/β-catenin or BMP signaling inhibited NSC differentiation and reduced the expression ofWnt3a, BMP2, and β-catenin nuclear proteins. In conclusion, HBO promotes differentiationof NSCs into neurons and oligodendrocytes and reduced the number of astrocytes in vitropossibly through regulation of Wnt3/β-catenin and BMP2 signaling pathways. HBO may serveas a potential therapeutic strategy for treating HIE.