title: Refinement of a model of acquired epilepsy for identification and validation of biomarkers of epileptogenesis in rats.
abstract: In rodent models in which status epilepticus (SE) is used to induce epilepsy, typically most animals develop spontaneous recurrent seizures (SRS). The SE duration for induction of epileptogenesis depends on the type of SE induction. In models with electrical SE induction, the minimum duration of SE to induce epileptogenesis in >90% of animals ranges from 3-4h. A high incidence of epilepsy is an advantage in the search of antiepileptogenic treatments, whereas it is a disadvantage in the search for biomarkers of epileptogenesis, because it does not allow a comparison of potential biomarkers in animals that either develop or do not develop epilepsy. The aim of this project was the refinement of an established SE rat model so that only ~50% of the animals develop epilepsy. For this purpose, we used an electrical model of SE induction, in which a self-sustained SE develops after prolonged stimulation of the basolateral amygdala. Previous experiments had shown that the majority of rats develop SRS after 4-h SE in this model so that the SE reduced duration to 2.5h by administering diazepam. This resulted in epilepsy development in only 50% of rats, thus reaching the goal of the project. The latent period to onset of SRS wa s >2weeks in most rats. Development of epilepsy could be predicted in most rats by behavioral hyperexcitability, whereas seizure threshold did not differentiate rats that did and did not develop SRS. The refined SE model may offer a platform to identify and validate biomarkers of epileptogenesis.
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Brandt
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany.
authors.forename: Vladan
authors.initials: V
authors.lastname: Rankovic
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Töllner
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klee
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Bröer
authors.affiliation: Department of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine Hannover, 30559 Hannover, Germany; Center for Systems Neuroscience, 30559 Hannover, Germany. Electronic address: wolfgang.loescher@tiho-hannover.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
mesh_terms: D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe; D005260:Female; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000209:etiology* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers
keywords: Basolateral amygdala; Seizure threshold; Seizures; Status epilepticus; Temporal lobe epilepsy