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Published on: February 27, 2018
2-Deoxyglucose terminates pilocarpine-induced status epilepticus in neonatal rats
Remi Janicot1, Carl E Stafstrom1, Li-Rong Shao1
1Division of Pediatric Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Insights
The glycolytic inhibitor 2-deoxyglucose (2-DG) effectively stopped neonatal seizures in rats. This metabolic approach offers a promising new treatment for drug-resistant neonatal status epilepticus (SE).
Area of Science:
- Neuroscience
- Metabolic Medicine
- Pediatric Neurology
Background:
- Neonatal status epilepticus (SE) is a critical condition with limited treatment options.
- Up to 50% of neonates with SE are resistant to current antiseizure medications.
- Novel therapeutic strategies are urgently needed for refractory neonatal SE.
Purpose of the Study:
- To investigate the efficacy of 2-deoxyglucose (2-DG), a glycolytic inhibitor, as a potential treatment for neonatal SE.
- To compare the antiseizure effects of 2-DG with conventional drugs like phenobarbital and levetiracetam.
- To explore a metabolic approach for controlling neonatal seizures.
Main Methods:
- Status epilepticus (SE) was induced in neonatal rats (postnatal day 10-17) using pilocarpine.
- Video-electroencephalography (V-EEG) monitored seizure activity.
- 2-DG, phenobarbital, or levetiracetam was administered intraperitoneally after 30 minutes of SE.
Main Results:
- 2-DG administration rapidly suppressed both behavioral and electrographic seizures within 10-15 minutes in a dose-dependent manner.
- Phenobarbital and levetiracetam also effectively terminated SE in neonatal rats.
- 2-DG demonstrated a rapid onset of action in controlling seizure activity.
Conclusions:
- The glycolysis inhibitor 2-DG effectively reduces neuronal hyperexcitability and suppresses ongoing seizure activity in neonatal rats.
- 2-DG shows potential as a novel therapeutic agent for neonatal status epilepticus.
- This metabolic strategy may offer a viable alternative for treating drug-resistant neonatal SE.
Objective:
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).
Methods:
SE was induced by pilocarpine (300 mg/kg, intraperitoneally [ip]) in neonatal Sprague Dawley rats (postnatal day 10 [P10]-P17) and was monitored by video-electroencephalography (V-EEG). After 30 minutes 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.
Results:
Once SE became sustained, administration of 2-DG (50, 100, or 500 mg/kg, ip) consistently stopped behavioral and electrographic seizures within 10-15 minutes; lower doses took longer (25-30 minutes) to stop SE, demonstrating a dose-dependent effect. Administration of phenobarbital (30 mg/kg, ip) or levetiracetam (100 mg/kg, ip) also stopped SE within 10-15 minutes in neonatal rats.
Significance:
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.
