Recurrent neonatal seizures increase tonic inhibition and respond to enhancers of δ-containing GABAA receptors.

ABSTRACT: About one-third of neonatal seizures do not respond to the first-line anticonvulsant phenobarbital, which activates phasic inhibition and whose effectiveness decreases over time. Whether enhancing tonic inhibition can treat refractory seizures or status epilepticus in neonates remains uncertain. We evaluated the effect of recurrent seizure-like events (SLE) on α5- and δ-GABAA receptor (α5- and δ-GABAAR) subunit expression and tonic inhibition in neonatal C57BL/6J mice (P6-9, both sexes) using acute brain slices. We investigated the impact of THIP (gaboxadol) on neonatal behavioral seizures, neuronal apoptosis, and neurodegeneration in vivo. We found neonatal neocortical expression of α5- and δ-GABAAR subunits. Blocking α5-GABAARs with L-655,708 did not affect acute neonatal SLE, whereas en

SUBMITTER: Liddiard GT 

PROVIDER: S-EPMC12643521 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature