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Postnatal interleukin-1β enhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats

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Abstract

Febrile seizures (FS) are recognized as an antecedent to the development of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), but it is unclear whether prolonged FS are a direct cause of TLE-HS. Here, we used a rat model of infantile FS to study the effects of inflammatory cytokines on seizure susceptibility and neuronal death in adults. Prolonged hyperthermia-induced seizures (pHS) were induced in male Lewis rats at post natal day (P) 10. Cytokines were administered twice intranasally, once immediately after pHS and once the following day. The effects of intranasal interleukin (IL)-1β or tumor necrosis factor (TNF) α were tested in rats undergoing a single episode of pHS (P10) and in rats undergoing repeated pHS (P10 and P12). Seizure susceptibility was tested at P70–73 by quantifying the seizure onset time (SOT) after kainic acid administration, and neuronal cell injury and gliosis in adulthood. SOT significantly reduced in rats receiving IL-1β together with repeated pHS, whereas no significant effects were seen in rats receiving IL-1β after a single pHS episode, or in rats receiving TNFα. Hippocampal neuronal cell loss was observed in the CA3 region of rats receiving IL-1β together with repeated pHS; however, there was no significant change in gliosis among each group. Our results are consistent with the hypothesis that excessive production of IL-1β after repeated prolonged FS can enhance adult seizure susceptibility and neuronal cell death, and might contribute to the development of TLE-HS.

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Acknowledgments

This study was supported by a Grant-in-Aid for Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology (No.22591132), a Research Grant from the Japan Epilepsy Research Foundation, and a Research Promotion Award from Ehime University. We are grateful to the staff of the Animal Center of INCS of Ehime University for their gentle care of our animals, and Takeshi Kiyoi for help with histological staining.

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Authors and Affiliations

  1. Department of Pediatrics, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan

    Mitsumasa Fukuda, Hitomi Hino, Yuka Suzuki & Eiichi Ishii

  2. Ehime Proteo-Medicine Research Center, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, Japan

    Hisaaki Takahashi

  3. Ehime Rehabilitation Center for Children, 1235 Tanokubo, Toon, Ehime, Japan

    Takehiko Morimoto

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  1. Mitsumasa Fukuda
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  2. Hitomi Hino
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  3. Yuka Suzuki
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  4. Hisaaki Takahashi
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Correspondence to Mitsumasa Fukuda.

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Fukuda, M., Hino, H., Suzuki, Y. et al. Postnatal interleukin-1β enhances adulthood seizure susceptibility and neuronal cell death after prolonged experimental febrile seizures in infantile rats. Acta Neurol Belg 114, 179–185 (2014). https://doi.org/10.1007/s13760-013-0246-y

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