title: Forebrain-independent generation of hyperthermic convulsions in infant rats.
abstract: Febrile seizures are the most common type of convulsive events in children. It is generally assumed that the generalization of these seizures is a result of brainstem invasion by the initial limbic seizure activity. Using precollicular transection in 13-day-old rats to isolate the forebrain from the brainstem, we demonstrate that the forebrain is not required for generation of tonic-clonic convulsions induced by hyperthermia or kainate. Compared with sham-operated littermate controls, latency to onset of convulsions in both models was significantly shorter in pups that had undergone precollicular transection, indicating suppression of the brainstem seizure network by the forebrain in the intact animal. We have shown previously that febrile seizures are precipitated by hyperthermia-induced respiratory alkalosis. Here, we show that triggering of hyperthermia-induced hyperventilation and consequent convulsions in transected animals are blocked by diazepam. The present data suggest that the role of endogenous brainstem activity in triggering tonic-clonic seizures should be re-evaluated in standard experimental models of limbic seizures. Our work sheds new light on the mechanisms that generate febrile seizures in children and, therefore, on how they might be treated.
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Alexey S
authors.initials: AS
authors.lastname: Pospelov
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Alexey Y
authors.initials: AY
authors.lastname: Yukin
authors.affiliation: Departments of Psychology and Biology, University of Iowa, Iowa City, Iowa, U.S.A.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Blumberg
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Martin
authors.initials: M
authors.lastname: Puskarjov
authors.affiliation: Department of Biosciences and Neuroscience Center, University of Helsinki, Helsinki, Finland.
authors.forename: Kai
authors.initials: K
authors.lastname: Kaila
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000927:Anticonvulsants / Q000627:therapeutic use; D001831:Body Temperature / Q000502:physiology; D003714:Denervation; D003975:Diazepam / Q000627:therapeutic use; D004195:Disease Models, Animal; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D006979:Hyperthermia, Induced / Q000009:adverse effects*; D007608:Kainic Acid / Q000633:toxicity; D008297:Male; D016548:Prosencephalon / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000188:drug therapy / Q000209:etiology*; D013997:Time Factors
chemical_list: D000927:Anticonvulsants; D018690:Excitatory Amino Acid Agonists; D003975:Diazepam; D007608:Kainic Acid
keywords: Brainstem; Diazepam; Febrile seizures; Kainic acid; Precollicular transection