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Postnatal interleukin-1β administration after experimental prolonged febrile seizures enhances epileptogenesis in adulthood

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Abstract

It remains unclear whether prolonged febrile seizures (pFS) in childhood facilitate mesial temporal lobe epilepsy (MTLE) in adulthood. Interleukin (IL)-1β is associated with seizures in children and immature animal models. Here, we use a rat model of pFS to study the effects of IL-1β on adult epileptogenesis, hippocampal damage, and cognition. We produced prolonged hyperthermia-induced seizures on postnatal days (P) 10–11 and administered IL-1β or saline intranasally immediately after the seizures. Motor and cognitive functions were assessed at P85 using rotarod and passive avoidance tests. Electroencephalogram recordings were conducted at P90 and P120. Hippocampal CA1 and CA3 neurons and gliosis were quantified at the end of the experiment. Spontaneous seizure incidence was significantly greater in rats that had received IL-1β than in those that had received saline or those without hyperthermia-induced seizures (p < 0.05). Seizure frequency did not differ significantly between the three groups and no motor deficits were observed. Passive avoidance learning was impaired in rats that received IL-1β compared with controls (p < 0.05), but was not different from that in rats that received saline. Hippocampal cell numbers and gliosis did not differ between the three groups. These results indicate that neuronal loss and gliosis are not prerequisites for the epileptogenic process that follows pFS. Our results suggest that infantile pFS combined with IL-1β overproduction can enhance adulthood epileptogenesis, and might contribute to the development of MTLE.

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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) and The Setsuro Fujii Memorial Osaka Foundation for Promotion of Fundamental Medical Research, and a Research Grant of the Japan Epilepsy Research Foundation. We are grateful to the staff of the Animal Center of INCS of Ehime University for their care of our animals, and Takeshi Kiyoi for help with histological staining.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All experimental procedures conformed to the guidelines from the Ministry of Education of Japan and were approved by the animal experimental committee of our University. This article does not contain any studies with animals performed by any of the authors.

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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, Masanori Ito, Yoshiaki Yano, Ryota Motoie, Akiko Yano, Yuka Suzuki & Eiichi Ishii

  2. Department of Molecular and Cellular Physiology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan

    Hisaaki Takahashi

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  1. Mitsumasa Fukuda
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  2. Masanori Ito
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  3. Yoshiaki Yano
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  4. Hisaaki Takahashi
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  5. Ryota Motoie
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  6. Akiko Yano
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  7. Yuka Suzuki
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  8. Eiichi Ishii
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Correspondence to Mitsumasa Fukuda.

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Fukuda, M., Ito, M., Yano, Y. et al. Postnatal interleukin-1β administration after experimental prolonged febrile seizures enhances epileptogenesis in adulthood. Metab Brain Dis 30, 813–819 (2015). https://doi.org/10.1007/s11011-014-9648-7

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  • DOI: https://doi.org/10.1007/s11011-014-9648-7

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