title: Long-term modifications of epileptogenesis and hippocampal rhythms after prolonged hyperthermic seizures in the mouse.
abstract: Complex febrile seizures are often reported in the history of patients with mesio-temporal lobe epilepsy (MTLE) but their role in its physiopathology remains controversial. We postulated that prolonged hyperthermic seizures might, as a "single-hit", modify the hippocampal rhythms, facilitate epileptogenesis and influence subsequent epilepsy when a second-hit already exists or subsequently occurs. To test this hypothesis, we examined the effects of hyperthermic seizures (30min at 40-41°C) at postnatal day 10 on hippocampal activity in C57BL/6J mice in comparison to their littermates in sham conditions (22°C), with or without another insult. Using local field potential, we observed an asymmetry in the hippocampal susceptibility to seize in hyperthermic conditions. When these mice were adult, an asymmetrical increase of low frequency power was also recorded in the hippocampus when compared to sham animals. Using two different "two-hit" protocols, no increase in seizures or hippocampal discharge frequency or duration was observed, either in mice with a genetic CA3 dysplasia (Dcx knockout), or in mice injected with kainate into the dorsal hippocampus at P60. However, in the latter condition, which is reminiscent of MTLE, the hyperthermic seizures accelerated epileptogenesis and decreased the power in the high frequency gamma band, as well as decreasing the coherence between hippocampi and the involvement of the contralateral hippocampus during hippocampal paroxysmal discharges. Our data suggest that a single episode of prolonged hyperthermic seizures does not induce per se, but accelerates epileptogenesis and could lead to an asymmetrical dysfunction in the hippocampal rhythmicity in both physiological and pathological conditions.
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France; CH Bourgoin-Jallieu, Hôpital Pierre Oudot, F-38317 Bourgoin-Jallieu, France. Electronic address: Sophie.Hamelin@ujf-grenoble.fr.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hamelin
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France; Synapcell, F-38000 Grenoble, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Pouyatos
authors.affiliation: Institut du Fer à Moulin, F-75005 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, F-75005 Paris, France; INSERM, UMRS 839, F-75005 Paris, France.
authors.forename: Reham
authors.initials: R
authors.lastname: Khalaf-Nazzal
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France.
authors.forename: Tanguy
authors.initials: T
authors.lastname: Chabrol
authors.affiliation: Institut du Fer à Moulin, F-75005 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, F-75005 Paris, France; INSERM, UMRS 839, F-75005 Paris, France.
authors.forename: Fiona
authors.initials: F
authors.lastname: Francis
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: David
authors.affiliation: INSERM, U836, F-38000 Grenoble, France; Univ. Grenoble Alpes, GIN, F-38000 Grenoble, France; CHU de Grenoble, Hôpital Michalon, F-38000 Grenoble, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Depaulis
mesh_terms: D000818:Animals; D003700:Delta Rhythm; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D005260:Female; D065818:Gamma Rhythm / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development* / Q000503:physiopathology*; D007608:Kainic Acid; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics; D009479:Neuropeptides / Q000172:deficiency / Q000235:genetics; D003294:Seizures, Febrile / Q000503:physiopathology*; D013826:Theta Rhythm
chemical_list: C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D007608:Kainic Acid
keywords: Early life seizures; Epileptogenesis; Febrile seizures; Hippocampal asymmetry; Hippocampal sclerosis; Hyperthermic seizures; Mesio-temporal lobe epilepsy