571 Effect of Neonatal Hypoxia/Ischemia on Gabaa Receptor Protein Expression

Abstract

Background and aims: Current therapeutic options for neonatal hypoxia/ischemia (HI) are limited to hypothermia and treatment of seizures. The principal function of the GABA system in mature brain is inhibition, however in neonatal brain GABA provides much of the excitatory drive. Thus whilst anticonvulsants augment GABA's inhibitory actions in mature brain, administration of GABAergic drugs to neonates may potentially exacerbate seizures and worsen HI brain injury. Furthermore changes in GABAA receptor expression will influence receptor pharmacology. We aimed to assess changes in protein expression of the GABAA receptor in the neonatal HI piglet. Methods: Newborn piglets were subjected to a 30 min HI insult and euthanased at 72 h. Brain tissue was collected from several brain regions and GABAA receptor α3 protein expression levels analysed by western blot. Results: Expression of α3 was significantly elevated in frontal cortex of HI animals without seizure; animals with seizure trended toward lower a3 expression. In occipital cortex, α3 expression was found to be diminished in all HI animals however presence of seizures was associated with significantly lower α3 expression. Conclusions: GABAA receptor α3 expression was significantly altered following neonatal HI; presence of seizures further changed this expression. Efficacy of anticonvulsants in neonatal brain may not only depend on regional and temporal maturation of GABAergic inhibitory function but also on GABAA receptor subunit expression following both HI and seizures. There is a critical need to develop effective treatment strategies specific to the neonatal HI brain.