Ethosuximide converts ictogenic neurons initiating absence seizures into normal neurons in a genetic model.
Absence epilepsy is a form of generalized epilepsy commonly seen in children. The neuronal process by which ethosuximide (ETX), a first choice anti-absence drug, prevents absence seizures is still unresolved. Recent clinical findings have indicated that focal cortical regions are involved during absence seizures. Consistently, it has been shown in genetic models of absence epilepsy that epileptic discharges arise from a delimited region of the cerebral cortex. Here, we made simultaneous in vivo electrocorticographic and intracellular recordings from the cortical focus of the genetic absence epilepsy rat from Strasbourg and examined the effects of systemic injection of ETX at a therapeutic concentration. We show that the interruption of seizures by ETX is correlated with a recovery, in the hyperactive focus neurons, of physiologic values of membrane potential, firing rate, and pattern, as measured in analogous neurons from nonepileptic rats. These data suggest that the anti-absence action of ETX results from the conversion of ictogenic cortical neurons into normal cortical neurons.
Polack
Pierre-Olivier
PO
INSERM UMR_S 667, Dynamique et physiopathologie des réseaux neuronaux, Paris, France.
Charpier
Stephane
S
D000200:Action Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000818:Animals; D001931:Brain Mapping / Q000379:methods / Q000523:psychology / Q000706:statistics & numerical data; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000706:statistics & numerical data; D004832:Epilepsy, Absence / Q000188:drug therapy* / Q000503:physiopathology; D005013:Ethosuximide / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008957:Models, Genetic; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013003:Somatosensory Cortex / Q000187:drug effects / Q000503:physiopathology
D005013:Ethosuximide