Transient ischemia facilitates neuronal chloride accumulation and severity of seizures. Issue 9 (5th July 2018)

• Record Type: Journal Article
• Authors: Blauwblomme, Thomas; Dzhala, Volodymyr; Staley, Kevin
• Is Part Of: Annals of clinical and translational neurology. Volume 5:Issue 9(2018)
• Page Start: 1048
• Page End: 1061
• Publication Date: 2018-07-05
• Subjects: Nervous system -- Diseases -- Periodicals; Neurology -- Periodicals; 616.8005
• DOI: 10.1002/acn3.617
• Languages: English
• ISSNs: 2328-9503

Abstract

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.