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

Abstract

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.

Epilepsy in Wolf‐Hirschhorn Syndrome (4p‐)

“…The LETM1 gene encodes a putative member of the Ca 2+ -binding protein, which controls Ca 2+ signaling and homeostasis (14). In addition, Br was reported to have a concentration-dependent effect to block low Ca 2+ -induced seizure discharges in rat brain slices (15). Thus Ca 2+ -binding proteins translated from the LETM1 gene may play an important role in seizures in WHS patients.…”

Action of antiepileptic drugs on neurons

“…A neurosteroid, ganaxolone, potentiates the action of GABA at low concentrations, and it directly activates the GABA A receptors at high concentrations [12]. Stiripentol, FBM, TPM, and bromide are also suggested to enhance GABAergic inhibition [13][14][15].…”

Biophysical Aspects of the Nonsynaptic Epileptiform Activity

“…In fact, in a recent case reported on the use of bumetanide for treatment of autism, the authors did not observe, at the dosage investigated, any side effect (Franciolini & Nonner, 1987). To overcome the severe side effects of bromide described (Meierkord et al, 2000), it is paramount that bromide be administered with care, that followup testing be carried out, and that serum bromide levels be monitored periodically. We also propose that effort should be directed to find anions or anionic compounds that can replace bromide with the aim of avoiding its side effects.…”