Activation Of HIF-1? And Notch Signaling Pathways Is Associated With Microglia And Inflammation In Temporal Lobe Epilepsy Models

Objective The inflammatory response mediated by microglia in the central nervous system is closely related to epilepsy.Notch and HIF-1? signaling play an important role in the microglial activation during hypoxia and there is cross-talk between Notch and HIF-1? signaling in some pathological environment.This study aimed to investigate whether Notch and HIF-1? signaling is involved in microglial activation and subsequent inflammation-related neuronal injury during the process of epileptogenesis in a rat model of temporal lobe epilepsy.Moreover,the relationship of Notch and HIF-1? signaling was also revealed.Method In our study,we performed western blotting,real-time quantitative PCR,immunohistochemistry and immunofluorescence labeling,and CoImmunoprecipitation.The inhibitors of Notch and HIF-1? signaling were intraperitoneally administered in the temporal lobe epilepsy rats.Results we found that the expression of Notch and HIF-1? signaling increased after status epilepticus and that the inhibitors of Notch and HIF-1? signaling could significantly inhibit the upregulation of signaling expression,the activation of microglia,and the release of proinflammatory cytokines.Likewise,the neuronal apoptosis and loss in the hippocampus after SE were attenuated by these inhibitors.Our results also revealed that HIF-1? physically bound NICD protein and modulated transcription and expression levels of Notch downstream target genes.Conclusions Our study demonstrated that HIF-1? and Notch signaling pathways play a key role in neuroinflammation and inflammation-related neuronal damage in epilepsy.In the acute of epilepsy,HIF-1? regulate Notch signaling and activate microglia under hypoxia.The inhibitors of HIF-1? and Notch signaling may become a novel prospective therapeutic agent for epilepsy.