title: Anti-epileptogenesis: Electrophysiology, diffusion tensor imaging and behavior in a genetic absence model.
abstract: The beneficial effects of chronic and early pharmacological treatment with ethosuximide on epileptogenesis were studied in a genetic absence epilepsy model comorbid for depression. It was also investigated whether there is a critical treatment period and treatment length. Cortical excitability in the form of electrical evoked potentials, but also to cortico-thalamo-cortical network activity (spike-wave discharges, SWD and afterdischarges), white matter changes representing extra cortico-thalamic functions and depressive-like behavior were investigated. WAG/Rij rats received either ethosuximide for 2 months (post natal months 2-3 or 4-5), or ethosuximide for 4 months (2-5) in their drinking water, while control rats drank plain water. EEG measurements were made during treatment, and 6 days and 2 months post treatment. Behavioral test were also done 6 days post treatment. DTI was performed ex vivo post treatment. SWD were suppressed during treatment, and 6 days and 2 months post treatment in the 4 month treated group, as well as the duration of AD elicited by cortical electrical stimulation 6 days post treatment. Increased fractional anisotropy in corpus callosum and internal capsula on DTI was found, an increased P8 evoked potential amplitude and a decreased immobility in the forced swim test. Shorter treatments with ETX had no large effects on any parameter. Chronic ETX has widespread effects not only within but also outside the circuitry in which SWD are initiated and generated, including preventing epileptogenesis and reducing depressive-like symptoms. The treatment of patients before symptom onset might prevent many of the adverse consequences of chronic epilepsy.
authors: Donders Centre for Cognition, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands. Electronic address: g.vanluijtelaar@donders.ru.nl.
authors: Gilles
authors: G
authors: van Luijtelaar
authors: Asht M
authors: AM
authors: Mishra
authors: Peter
authors: P
authors: Edelbroek
authors: Daniel
authors: D
authors: Coman
authors: Nikita
authors: N
authors: Frankenmolen
authors: Pauline
authors: P
authors: Schaapsmeerders
authors: Giulio
authors: G
authors: Covolato
authors: Nathan
authors: N
authors: Danielson
authors: Hannah
authors: H
authors: Niermann
authors: Kryzstof
authors: K
authors: Janeczko
authors: Anne
authors: A
authors: Kiemeneij
authors: Julija
authors: J
authors: Burinov
authors: Chhitij
authors: C
authors: Bashyal
authors: Madeline
authors: M
authors: Coquillette
authors: Annika
authors: A
authors: Lüttjohann
authors: Fahmeed
authors: F
authors: Hyder
authors: Hal
authors: H
authors: Blumenfeld
authors: Clementina M
authors: CM
authors: van Rijn
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003863:Depression / Q000503:physiopathology; D056324:Diffusion Tensor Imaging; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005013:Ethosuximide / Q000097:blood / Q000627:therapeutic use*; D005071:Evoked Potentials; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological; D013550:Swimming
chemical_list: D000927:Anticonvulsants; D005013:Ethosuximide
keywords: Afterdischarges; Antiepileptogenesis; Cortical focus theory; DTI; Depression; Electrical stimulation; Ethosuximide; Somatosensory cortex; WAG/Rij rats
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