Open AccessTransient ischemia facilitates neuronal chloride accumulation and severity of seizures
Author(s) -
Blauwblomme Thomas,
Dzhala Volodymyr,
Staley Kevin
Publication year - 2018
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.617
Subject(s) - bumetanide , phenobarbital , anticonvulsant , medicine , inhibitory postsynaptic potential , pharmacology , furosemide , epilepsy , carbamazepine , chloride , anesthesia , chemistry , ion transporter , biochemistry , organic chemistry , membrane , psychiatry
Objective Preceding oxygen glucose deprivation ( OGD ) and ongoing seizures have both been reported to increase neuronal chloride concentration ([Cl − ] i ), which may contribute to anticonvulsant failure by reversing the direction of chloride currents at inhibitory GABA A synapses. Methods The effects of OGD on [Cl − ] i , seizure activity, and anticonvulsant efficacy were studied in a chronically epileptic in vitro preparation. Results Seizures initially increased during OGD , followed by suppression. On reperfusion, seizure frequency and [Cl − ] i progressively increased, and phenobarbital efficacy was reduced. Bumetanide (10 μ mol/L) and furosemide (1 mmol/L) prevented or reduced the OGD induced [Cl − ] i increase. Phenobarbital efficacy was enhanced by bumetanide (10 μ mol/L). Furosemide (1 mmol/L ) suppressed recurrent seizures. Interpretation [Cl − ] i increases after OGD and is associated with worsened seizure activity, reduced efficacy of GABA ergic anticonvulsants, and amelioration by antagonists of secondary chloride transport.