Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices

Heinemann, Uwe; Franceschetti, Silvana; Hamon, Brigitte; Konnerth, Arthur; Yaari, Yoel

doi:10.1016/0006-8993(85)90338-5

Cited by 80 publications

(29 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that the various types of discharges used in the current experiments display a different sensitivity towards anticonvulsant drugs. The low Ca 2+ -induced epileptiform activity has been shown to be sensitive to substances altering membrane excitability such as valproic acid, phenytoin, carbamazepine and barbiturates but not to glutamate antagonists or to benzodiazepines (Heinemann et al 1985) in accordance with the assumption that synaptic transmission is of minor importance in this model. NaBr concentrationdependently reduced the frequency or blocked these discharges which suggests that it affects membrane excitability of nerve cells.…”

Section: Discussionsupporting

confidence: 59%

Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition

Meierkord

Grünig

Gutschmidt

et al. 2000

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

Results regarding the anticonvulsant potency of bromide have been questioned, and the mechanisms of its action are unclear. Using combined rat hippocampus-entorhinal cortex slices we analyzed the effects of NaBr on four types of epileptiform discharges in two different models of epilepsy, the low-Ca2+ and the low-Mg2+ model. NaBr concentration-dependently reduced the frequency and finally blocked the low Ca2+-induced discharges. Low Mg2+-induced short recurrent discharges were also reduced in a concentration-dependent manner. In the entorhinal cortex the frequency of seizure-like events was reduced by 3 and 5 mM and the discharges were blocked by 7 mM NaBr. Also, the late recurrent discharges in the entorhinal cortex which do not respond to most clinically employed anticonvulsants were reduced by concentrations of 10 and 15 mM and completely blocked by 30 mM NaBr. Using pH-sensitive microelectrodes different effects of NaBr were seen than those of acetazolamide on extracellular pH under control conditions and after stimulation. Acetazolamide at 1 mM caused a reversible acidification of delta pH: 0.2+/-0.14 at rest whereas no change on extracellular pH was seen with 5 mM NaBr. Acetazolamide increased the transient alkalosis induced by repetitive stimulation of the stratum radiatum in area CA1 and reduced the subsequent acidosis. NaBr also increased the alkalosis but had no effect on the subsequent acidosis. A significant increase in paired-pulse inhibition was seen in a paired-pulse stimulation protocol used to monitor the efficacy of GABAergic inhibition at concentrations of 5 mM NaBr. This finding was confirmed in whole-cell patch clamp recordings from cultured hippocampal neurons showing an increase in inhibitory postsynaptic current amplitude. In summary, our results suggest a broad-spectrum anticonvulsant activity which is likely to be caused by its effects on membrane excitability, by an increase in GABAergic inhibition and is less likely caused by its effects on extracellular pH.

show abstract

Section: Discussionsupporting

confidence: 59%

Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition

Meierkord

Grünig

Gutschmidt

et al. 2000

Naunyn-Schmiedeberg's Arch Pharmacol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Similar effects have also been reported by Heinemann et al [1985] in hippocampal slices exposed to ACSF containing 0.1 mM Ca2+. The mechanism underlying SSEB are unknown, however, since neurotransmission is blocked, an anticonvulsant effect must be dependent on an influence on the intrinsic ionic conductances underlying SSEB.…”

Section: Discuss I0 Nsupporting

confidence: 87%

Comparative action of flunarizine, phenytoin, carbamazepine and two calcium‐entry blockers on spontaneous epileptiforrn bursts in the low calcium‐hippocampal slice preparation

Ashton

Reid

Willems

et al. 1986

Drug Development Research

View full text Add to dashboard Cite

Ashton, D., K. Reid, R. Willems, R. Marrannes, and A. Wauquier: Comparative action of flunarizine, phenytoin, carbamazepine and two calcium-entry blockers on spontaneous epileptiform bursts in the low calcium-hippocampal slice preparation. Drug Dev. Res. a:397-405,1986 Exposure of hippocampal slices to a medium containing a low Ca2+-concentration and an increased concentration of Mg2+ and K+ resulted in the blockade of synaptic transmission and the development of spontaneous synchronized epileptiform bursts (SSEB) in area CA1. The SSEBs were measured extracellularly as a negative potential shift with superimposed population spikes. Flunarizine is a "Ca2+-entry blocker" with antiepileptic actions in humans. We compared flunarizine with two reference antiepileptics (phenytoin and carbamazepine) and two other "Ca2+-entry blockers" (verapamil and nimodipine) for their ability to reduce SSEBs. Flunarizine, which is insoluble in ACSF bathing medium, was applied in a nanodrop directly onto the CA1 region of the slice. All other drugs were applied in the bathing medium. changes in Ca2+ and K + did not occur before changes in potential, modulation of Ca2+ or K + channels in striatum pyrarnidale is unlikely to explain flunarizine's ability to reduce synchronized bursts. Further, the ability to block Ca2+ channels in the periphery appears to be unrelated to the ability to block SSEBs in this model. It is suggested that reduction of Na+ currents during depolarization may be the basis of the similar effects of phenytoin, carbamazepine and flunarizine in this model.

show abstract

“…This may be because the hippocampus is not a principal site of action of the antiabsence drugs or that it may not be involved in absence seizures. Valproate is effective against low-calcium seizures in hippocampal slices (Agopyan et al, 1985;Heinemann et al, 1985) and depresses evoked responses in the presence of penicillin in prepiriform slices (Voskuyl et al, 1975), but relatively high concentrations are required as in the present study. The increases in threshold appear to parallel reductions in burst rate, suggesting that common mechanisms are responsible for both effects.…”

Section: Discussionmentioning

confidence: 66%

Effects of Anticonvulsants on Penicillin‐Induced Bursting in Guinea Pig Hippocampal Slices

Schneiderman

Evans

1986

Epilepsia

View full text Add to dashboard Cite

The effects of y-aminobutyric acid (GABA) and six anticonvulsants on penicillin-induced bursting were compared in guinea pig hippocampal slices. GABA, phenobarbital, pentobarbital, phenytoin, and diazepam slowed and eventually blocked spontaneous bursts. Lowintensity stimulation at concentrations that blocked spontaneous activity still evoked synchronous all-or-none burst responses, although the threshold increased and the bursts were briefer. Sodium valproate had similar effects, but very high concentrations (-10 mM) were required. Ethosuximide paradoxically increased spontaneous burst rate. This model appears to be differentially susceptible to the actions of GABA and the anticonvulsants commonly used to treat tonic-clonic and partial seizures but not to the antiabsence drugs.

show abstract

Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices

Cited by 80 publications

References 16 publications

Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition

Sodium bromide: effects on different patterns of epileptiform activity, extracellular pH changes and GABAergic inhibition

Comparative action of flunarizine, phenytoin, carbamazepine and two calcium‐entry blockers on spontaneous epileptiforrn bursts in the low calcium‐hippocampal slice preparation

Effects of Anticonvulsants on Penicillin‐Induced Bursting in Guinea Pig Hippocampal Slices

Contact Info

Product

Resources

About