Early hypoactivity of hippocampal rhythms during epileptogenesis after prolonged febrile seizures in freely-moving rats

Feng, Bo; Tang, Yangshun; Chen, Bin; Xu, Zhenghao; Wang, Yi; Wu, Dang; Zhao, Huawei; Zhang, Shihong; Chen, Zhong

doi:10.1007/s12264-014-1524-2

Cited by 6 publications

(4 citation statements)

References 34 publications

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“…Using whole-cell patch clamp, similar alterations were seen in cultured rat cortical neurons subjected to hyperthermia (Wang et al 2011). Increased inhibitory pre-synaptic terminals were identified in CA3 neurons of P35 rats that were exposed to a prolonged FS paradigm at P8 (Feng et al 2015). Our data showing decreased AP threshold in WT and RH/+ neurons following A/PFE are consistent with these prior results.…”

Section: Discussionmentioning

confidence: 99%

Early-life febrile seizures worsen adult phenotypes in Scn1a mutants

Dutton

Dutt

Papale

et al. 2017

Experimental Neurology

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Mutations in the voltage-gated sodium channel (VGSC) gene SCN1A, encoding the Nav1.1 channel, are responsible for a number of epilepsy disorders including genetic epilepsy with febrile seizures plus (GEFS+) and Dravet syndrome (DS). Patients with SCN1A mutations often experience prolonged early-life febrile seizures (FSs), raising the possibility that these events may influence epileptogenesis and lead to more severe adult phenotypes. To test this hypothesis, we subjected 21-23-day-old mice expressing the human SCN1A GEFS+ mutation R1648H to prolonged hyperthermia, and then examined seizure and behavioral phenotypes during adulthood. We found that early-life FSs resulted in lower latencies to induced seizures, increased severity of spontaneous seizures, hyperactivity, and impairments in social behavior and recognition memory during adulthood. Biophysical analysis of brain slice preparations revealed an increase in epileptiform activity in CA3 pyramidal neurons along with increased action potential firing, providing a mechanistic basis for the observed worsening of adult phenotypes. These findings demonstrate the long-term negative impact of early-life FSs on disease outcomes. This has important implications for the clinical management of this patient population and highlights the need for therapeutic interventions that could ameliorate disease progression.

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Section: Discussionmentioning

confidence: 99%

Early-life febrile seizures worsen adult phenotypes in Scn1a mutants

Dutton

Dutt

Papale

et al. 2017

Experimental Neurology

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“…IL-1β concentration increases transiently after infantile FS, while the subsequent epileptogenesis is a long-term and dynamic process 31 32 . How does this transient change of IL-1β modify neuronal excitability in a long-term process?…”

Section: Discussionmentioning

confidence: 99%

Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling

Feng

Tang

Chen

et al. 2016

Sci Rep

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It remains unclear how infantile febrile seizures (FS) enhance adult seizure susceptibility. Here we showed that the transient increase of interleukin-1β (IL-1β) after prolonged FS promoted adult seizure susceptibility, which was blocked by interleukin-1 receptor antagonist (IL-1Ra) within a critical time window. Postnatal administered IL-1β alone mimicked the effect of FS on adult seizure susceptibility. IL-1R1 knockout mice were not susceptible to adult seizure after prolonged FS or IL-1β treatment. Prolonged FS or early-life IL-1β treatment increased the expression of cannabinoid type 1 receptor (CB1R) for over 50 days, which was blocked by IL-1Ra or was absent in IL-1R1 knockout mice. CB1R antagonist, knockdown and endocannabinoid synthesis inhibitor abolished FS or IL-1β-enhanced seizure susceptibility. Thus, this work identifies a pathogenic role of postnatal IL-1β/IL-1R1 pathway and subsequent prolonged prominent increase of endocannabinoid signaling in adult seizure susceptibility following prolonged FS, and highlights IL-1R1 as a potential therapeutic target for preventing the development of epilepsy after infantile FS.

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“…Schuchmann et al [19] developed another animal model using a warm chamber as the heat source to raise the body temperature to an appropriate level. In our study, we chose the latter because we found that the warm chamber has lower mortality and fewer burns than heated air [38,40,64,65]. Besides, Dube et al [14] and Gassen et al [66] used mouse FS models, facilitating the use of genetically mutant mice and other specific techniques.…”

Section: Experimental Febrile Seizure Modelsmentioning

confidence: 99%

Generation of Febrile Seizures and Subsequent Epileptogenesis

Feng

Chen

2016

Neurosci. Bull.

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Febrile seizures (FSs) occur commonly in children aged from 6 months to 5 years. Complex (repetitive or prolonged) FSs, but not simple FSs, can lead to permanent brain modification. Human infants and immature rodents that have experienced complex FSs have a high risk of subsequent temporal lobe epilepsy. However, the causes of FSs and the mechanisms underlying the subsequent epileptogenesis remain unknown. Here, we mainly focus on two major questions concerning FSs: how fever triggers seizures, and how epileptogenesis occurs after FSs. The risk factors responsible for the occurrence of FSs and the epileptogenesis after prolonged FSs are thoroughly summarized and discussed. An understanding of these factors can provide potential therapeutic targets for the prevention of FSs and also yield biomarkers for identifying patients at risk of epileptogenesis following FSs.

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Early hypoactivity of hippocampal rhythms during epileptogenesis after prolonged febrile seizures in freely-moving rats

Cited by 6 publications

References 34 publications

Early-life febrile seizures worsen adult phenotypes in Scn1a mutants

Early-life febrile seizures worsen adult phenotypes in Scn1a mutants

Transient increase of interleukin-1β after prolonged febrile seizures promotes adult epileptogenesis through long-lasting upregulating endocannabinoid signaling

Generation of Febrile Seizures and Subsequent Epileptogenesis

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