2-Deoxyglucose terminates pilocarpine-induced status epilepticus in neonatal rats.

Abstract

Neonatal status epilepticus (SE) is a life-threatening medical emergency. Unfortunately, up to 50% of neonates with SE are resistant to current antiseizure drugs, highlighting the need for better treatments. This study aims to explore a novel metabolic approach as a potential alternative treatment to control neonatal SE, using the glycolytic inhibitor 2-deoxyglucose (2-DG). SE was induced by pilocarpine (300mg/kg, intraperitoneally [ip]) in neonatal Sprague Dawley rats (postnatal day 10 [P10]-P17) and was monitored by video-electroencephalography (V-EEG). After 30minutes of SE, 2-DG or one of two conventional antiseizure drugs with different mechanisms of action, phenobarbital or levetiracetam, was administrated ip, and V-EEG recording was continued for ~60 additional minutes. The time to seizure cessation after drug injection, EEG scores, and power spectra before and after drug or saline treatment were used to assess drug effects. Once SE became sustained, administration of 2-DG (50, 100, or 500mg/kg, ip) consistently stopped behavioral and electrographic seizures within 10-15minutes; lower doses took longer (25-30minutes) to stop SE, demonstrating a dose-dependent effect. Administration of phenobarbital (30mg/kg, ip) or levetiracetam (100mg/kg, ip) also stopped SE within 10-15minutes in neonatal rats. Our results suggest that the glycolysis inhibitor 2-DG acts quickly to reduce neuronal hyperexcitability and effectively suppress ongoing seizure activity, which may provide translational value in the treatment of neonatal SE.