Effects of antiepileptic drugs on refractory seizures in the intact immature corticohippocampal formation in vitro.
OBJECTIVE
We developed a new in vitro preparation of immature rats, in which intact corticohippocampal formations (CHFs) depleted in magnesium ions become progressively epileptic. The better to characterize this model, we examined the effects of 14 antiepileptic drugs (AEDs) currently used in clinical practice.


METHODS
Recurrent ictal-like seizures (ILEs, four per hour) were generated in intact CHFs of P7-8 rats, and extracellular recordings were performed in the hippocampus and neocortex. AEDs were applied at clinically relevant concentrations (at least two), during 30 min after the third ILE. Their ability to prevent or to delay the next ILE was examined.


RESULTS
Valproic acid and benzodiazepines (clobazam and midazolam) but also phenobarbital and levetiracetam prevent the occurrence of seizures. In contrast, usual concentrations of carbamazepine (CBZ), phenytoin, vigabatrin, tiagabine, gabapentin, lamotrigine (LTG), topiramate, felbamate, and ethosuximide did not suppress ILEs. In addition, LTG and CBZ aggravate seizures in one third of the cases.


CONCLUSIONS
This intact in vitro preparation in immature animals appears to be quite resistant to most AEDs. Blockade of seizures was achieved with drugs acting mainly at the gamma-aminobutyric acid (GABA)A-receptor site but not with those that increase the amount of GABA. Drugs with a broad spectrum of activity are efficient but not those preferentially used in partial seizures or absences. We suggest that this preparation may correspond to a model of epilepsy with generalized convulsive seizures and could be helpful to develop new AEDs for refractory infantile epilepsies.
Quilichini
Pascale Paule
PP
INMED-INSERM U29, Marseille, France.
Diabira
Diabé
D
Chiron
Catherine
C
Milh
Mathieu
M
Ben-Ari
Yehezkel
Y
Gozlan
Henri
H
D000367:Age Factors; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D004827:Epilepsy / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008275:Magnesium Deficiency / Q000503:physiopathology; D008297:Male; D019579:Neocortex / Q000187:drug effects* / Q000503:physiopathology; D051381:Rats
D000927:Anticonvulsants