Drug Week via NewsEdge :

2008 JUL 11 - (NewsRx.com) -- A new study, 'Standard antiepileptic drugs fail to block epileptiform activity in rat organotypic hippocampal slice cultures,' is now available (see also Epilepsy). "Earlier studies had demonstrated that tonic-clonic seizure-like events (SLEs) resembling electrographic correlates of limbic seizures in animals and humans can be induced in organotypic hippocampal slice cultures (OHSCs). We have explored OHSCs for their suitability to serve as in vitro models of limbic seizures for studying seizure mechanisms and screening new antiepileptic compounds," scientists in Berlin, Germany report.

"EXPERIMENTAL APPROACH: OHSCs were cultivated according to the interface method. Neuronal activity and extracellular potassium concentration were recorded under submerged conditions. SLEs were induced by lowering magnesium concentration or by applying the potassium channel blocker 4-aminopyridine. The effects of standard antiepileptic drugs (AEDs), carbamazepine, phenytoin, valproic acid, clonazepam, diazepam and phenobarbital sodium on SLEs were analysed. In more than 93% of OHSCs, AEDs did not prevent the induction of SLEs or stop ongoing seizure activity even when toxic concentrations were applied. This pharmacoresistance was independent of the method of seizure provocation, postnatal age at explantation (P2-P10) and cultivation time in vitro (2 months). SLEs were reversibly blocked by glutamate antagonists or the GABA(A)-agonist muscimol. We present a simple to establish in vitro model of tonic-clonic SLEs that is a priori pharmacoresistant and thus has an advantage over animal models of pharmacoresistant seizures in which responders and non-responders can be sorted out only after an experiment," wrote K. Albus and colleagues, Charite University.

The researchers concluded: "OHSCs could be suitable for exploring mechanisms of pharmacoresistant seizures and be used for the identification of new anticonvulsive compounds eventually effective in drug refractory epilepsy."

Albus and colleagues published their study in British Journal of Pharmacology (Standard antiepileptic drugs fail to block epileptiform activity in rat organotypic hippocampal slice cultures. British Journal of Pharmacology, 2008;154(3):709-24).

For more information, contact K. Albus, Institut fur Neurophysiologie, Johannes Muller Center of Physiology, CCM, Charite-Universitatsmedizin Berlin, Berlin, Germany.

Publisher contact information for the British Journal of Pharmacology is: Nature Publishing Group, Macmillan Building, 4 Crinan St., London N1 9XW, England.

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