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Bumetanide reduces seizure progression and the development of pharmacoresistant status epilepticus
Author(s) -
Sivakumaran Sudhir,
Maguire Jamie
Publication year - 2016
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.13270
Subject(s) - bumetanide , status epilepticus , ictal , anticonvulsant , epilepsy , diazepam , chemistry , pharmacology , kainic acid , in vivo , pilocarpine , hippocampus , neuroscience , endocrinology , cotransporter , medicine , psychology , biology , biochemistry , receptor , glutamate receptor , microbiology and biotechnology , organic chemistry , sodium
Summary Objective We investigated the role of chloride homeostasis in seizure progression and development of pharmacoresistant status epilepticus ( SE ) by pharmacologically targeting the Na‐K‐Cl cotransporter ( NKCC 1) with bumetanide. We also investigated the ability of bumetanide to restore the efficacy of diazepam following SE . Methods Kainic acid ( KA )–induced SE in vivo and 0‐Mg 2+ ‐induced seizure‐like events ( SLE s) in vitro were monitored using electroencephalography ( EEG ) recordings in freely moving adult male mice and extracellular field potential recordings in acute entorhinal cortex‐hippocampus slices, respectively. The ability of bumetanide to decrease epileptiform activity and prevent the development of pharmacoresistance to diazepam following SE was evaluated. Results Bumetanide treatment significantly reduced KA ‐induced ictal activity in vivo and SLE s in vitro. In addition, bumetanide restored the efficacy of diazepam in decreasing ictal activity following SE in both the in vivo and in vitro models. Significance Our data demonstrate an anticonvulsant effect of bumetanide on KA ‐induced seizures in adult mice, suggesting a role for chloride plasticity in seizure progression. These data also demonstrate that the erosion of inhibition during seizure progression could underlie the development of pharmacoresistant SE and implicate a role for chloride plasticity in this process.