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HMGB1-TLR4 Axis Plays a Regulatory Role in the Pathogenesis of Mesial Temporal Lobe Epilepsy in Immature Rat Model and Children via the p38MAPK Signaling Pathway

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Abstract

The HMGB1-TLR4 axis is activated in adult mouse models of acute and chronic seizure. Nevertheless, whether HMGB1 was involved in the pathogenesis of mesial temporal lobe epilepsy (MTLE) remains unknown. In this study, we first measured the dynamic expression patterns of HMGB1 and TLR4 in the hippocampi of a rat model and in children with MTLE, as well as the levels of TNF-α and IL-1β. In addition, HMGB1 was added to mimic the process of inflammatory response in neurons. Neuronal somatic size and dendritic length were measured by immunohistochemistry and digital imaging. The results showed that the expression of HMGB1 and TLR4 as well as the levels of TNF-α and IL-1β were higher in the three stages of MTLE development in the rat model and in the children with MTLE. HMGB1 increased the levels of TNF-α and IL-1β, upregulated the protein level of p-p38MAPK and promoted the growth of cell somatic size and dendritic length in neurons. Pre-treatment with p38MAPK inhibitor SB203580 decreased the levels of TNF-α and IL-1β, while downregulation of TLR4 significantly reduced HMGB1-induced p38MAPK signaling pathway activation. These data demonstrated that the HMGB1-TLR4 axis may play an important role in the pathogenesis of MTLE via the p38MAPK signaling pathway.

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    Authors and Affiliations

    1. Nursing Department, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, 453100, China

      Weihong Yang

    2. Department of Pediatrics, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, 453100, China

      Jing Li

    3. Neonatology Department, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, 453100, China

      Yun Shang & Jipeng Shi

    4. PICU, The First Affiliated Hospital of Xinxiang Medical College, No. 88 Jian Kang Road, Xinxiang, 453100, China

      Li Zhao, Mingying Wang & Shujun Li

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    1. Weihong Yang
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    Weihong Yang and Jing Li have contributed equally to the study.

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    Yang, W., Li, J., Shang, Y. et al. HMGB1-TLR4 Axis Plays a Regulatory Role in the Pathogenesis of Mesial Temporal Lobe Epilepsy in Immature Rat Model and Children via the p38MAPK Signaling Pathway. Neurochem Res 42, 1179–1190 (2017). https://doi.org/10.1007/s11064-016-2153-0

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    • DOI: https://doi.org/10.1007/s11064-016-2153-0

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