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Published on: June 12, 2018
Postnatal interleukin-1β administration after experimental prolonged febrile seizures enhances epileptogenesis in
Mitsumasa Fukuda1, Masanori Ito, Yoshiaki Yano
1Department of Pediatrics, Ehime University Graduate School of Medicine, 454 Shitsukawa, Toon, Ehime, 791-0295, Japan, fukumits@m.ehime-u.ac.jp.
Insights
Infantile prolonged febrile seizures (pFS) combined with elevated Interleukin-1β (IL-1β) may increase adult epilepsy risk. This study found IL-1β enhanced seizure incidence and impaired learning in a rat model, without causing brain damage.
Area of Science:
- Neuroscience
- Epileptology
- Developmental Neuroscience
Background:
- The link between childhood prolonged febrile seizures (pFS) and adult mesial temporal lobe epilepsy (MTLE) is not fully understood.
- Interleukin-1β (IL-1β) is implicated in pediatric seizures and animal models.
Purpose of the Study:
- To investigate the role of IL-1β in adult epileptogenesis following infantile pFS using a rat model.
- To assess the impact of IL-1β on hippocampal damage and cognitive function after pFS.
Main Methods:
- Induced prolonged hyperthermia-induced seizures in rats on postnatal days 10-11.
- Administered IL-1β or saline intranasally post-seizure.
- Evaluated motor and cognitive functions, performed EEG recordings, and quantified hippocampal neurons and gliosis.
Main Results:
- Rats receiving IL-1β post-pFS showed significantly higher spontaneous seizure incidence in adulthood.
- Cognitive impairment in passive avoidance learning was observed in the IL-1β group.
- No significant differences in seizure frequency, motor deficits, hippocampal cell numbers, or gliosis were found between groups.
Conclusions:
- Neuronal loss and gliosis are not necessary for epileptogenesis following pFS.
- Infantile pFS coupled with IL-1β overproduction may promote adult epileptogenesis and contribute to MTLE development.
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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