Lacosamide decreases neonatal seizures without increasing apoptosis

Area of Science:

• Neuroscience
• Pharmacology
• Developmental Biology

Background:

• Neonatal seizures often resist standard treatments like phenobarbital.
• Phenobarbital's limited efficacy in neonates is linked to GABA's depolarizing action due to high intracellular chloride.
• Alternative anticonvulsants not reliant on GABAergic modulation are needed for neonatal seizure treatment.

Purpose of the Study:

• To investigate lacosamide's efficacy in reducing neonatal seizures.
• To assess whether lacosamide increases apoptosis (programmed cell death) in the neonatal brain.

Main Methods:

• In vitro: Tested lacosamide on mouse neocortical slices challenged with 4-aminopyridine.
• In vivo: Evaluated lacosamide's effect on kainic acid-induced seizures in neonatal mice.
• Apoptosis was measured using TUNEL assay and cleaved-caspase 3 staining.

Main Results:

• Lacosamide dose-dependently reduced seizure-like activity in neonatal and adult mouse brain slices.
• In vivo, lacosamide decreased the duration and frequency of neonatal seizures.
• Lacosamide did not elevate apoptosis in the neocortex, either in vitro or in vivo.

Conclusions:

• Lacosamide effectively reduces neonatal seizures in mice without causing acute apoptosis.
• These findings suggest lacosamide as a promising therapeutic option for neonatal seizures, offering a potentially safer profile than current treatments.