Transient ischemia facilitates neuronal chloride accumulation and severity of seizures. Issue 9 (5th July 2018) - Blauwblomme, Thomas
Abstract: 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 GABAA 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 GABAergic anticonvulsants, and amelioration by antagonists of secondary chloride transport.