Notch-1 Signaling Regulates Microglia Activation via NF-κB Pathway after Hypoxic Exposure In Vivo and In Vitro

摘要: Neuroinflammation mediated by the activated microglia is suggested to play a pivotal role in pathogenesis of hypoxic brain injury; however, underlying mechanism activation remains unclear. Here, we show that canonical Notch signaling orchestrates after exposure which closely associated with multiple pathological situations brain. Notch-1 and Delta-1 expression primary BV-2 microglial cells was significantly elevated hypoxia. Hypoxia-induced further confirmed concomitant increase translocation intracellular receptor domain (NICD), together RBP-Jκ target gene Hes-1 expression. Chemical inhibition N-[N-(3,5-difluorophenacetyl)-1-alany1- S-phenyglycine t-butyl ester (DAPT), γ-secretase inhibitor, effectively reduced hypoxia-induced upregulated most inflammatory mediators. also NF-κB/p65 translocation. Remarkably, suppressed TLR4/MyD88/TRAF6 pathways. In vivo, were observed cerebrum postnatal rats injury. Most interestingly, upregulation NF-κB immunoexpression prevented when given DAPT pretreatment underscoring interrelationship between Taken together, conclude involved regulating hypoxia partly through cross talk TLR4/MyD88/TRAF6/NF-κB Therefore, may serve as prospective for known be implicated damage developing