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Notch Signaling Regulates Microglial Activation and Inflammatory Reactions in a Rat Model of Temporal Lobe Epilepsy

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Abstract

The inflammatory response mediated by microglia in the central nervous system is closely related to epilepsy. Notch signaling plays an important role in the microglial activation during hypoxia. This study aimed to investigate whether Notch 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. By using western blotting, real-time quantitative PCR, immunohistochemistry and immunofluorescence labeling, we found that the expression of Notch signaling increased after status epilepticus and that a γ-secretase inhibitor could significantly inhibit the upregulation of Notch signaling, the activation of microglia, and the release of proinflammatory cytokines. Likewise, the neuronal apoptosis and loss in the hippocampus after SE were attenuated by the γ-secretase inhibitor. These results suggest that Notch signaling plays a key role in neuroinflammation and inflammation-related neuronal damage in epilepsy, and γ-secretase inhibitors may become a novel prospective therapeutic agent for epilepsy.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 81571734 and 81771819).

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  1. Lei Wu, Yushuang Li and Minhua Yu have contributed equally to this work.

Authors and Affiliations

  1. Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, 430071, Hubei, People’s Republic of China

    Lei Wu, Yushuang Li, Minhua Yu, Fei Yang, Mengqi Tu & Haibo Xu

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  1. Lei Wu
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Correspondence to Haibo Xu.

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Wu, L., Li, Y., Yu, M. et al. Notch Signaling Regulates Microglial Activation and Inflammatory Reactions in a Rat Model of Temporal Lobe Epilepsy. Neurochem Res 43, 1269–1282 (2018). https://doi.org/10.1007/s11064-018-2544-5

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