Transient ischemia facilitates neuronal chloride accumulation and severity of seizures.

ABSTRACT: ObjectivePreceding 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 GABAA synapses.MethodsThe effects of OGD on [Cl-]i, seizure activity, and anticonvulsant efficacy were studied in a chronically epileptic in vitro preparation.ResultsSeizures initially increased during OGD, followed by suppression. On reperfusion, seizure frequency and [Cl-]i progressively increased, and phenobarbital efficacy was reduced. Bumetanide (10 ?mol/L) and furosemide (1 mmol/L) prevented or reduced the OGD induced [Cl-]i increase. Phenobarbital efficacy was enhanced by bumetanide (10 ?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 GABAergic anticonvulsants, and amelioration by antagonists of secondary chloride transport.

SUBMITTER: Blauwblomme T 

PROVIDER: S-EPMC6144438 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature