Effects of glutamate and gamma-aminobutyric acid receptor modulation on the developing brain


Dalia Zykutė1, Jokūbas Liutkus1

1Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine, Kaunas, Lithuania


The repercussions of early, long-lasting anaesthesia on child brain function are not established. Nervous system development continues throughout childhood, therefore central nervous system agents could have permanent effects on neurological functions. The early development of synaptic junctions and formation of neural networks, selective synapse elimination and maturation are important for the establishment of proper brain function.  Therefore, the use of pharmacological agents on an immature brain could cause impairment of proper neurological organization. Neurotransmitters gamma-aminobutyric acid (GABA) and glutamate play an important role in various stages of development – from cell proliferation to proper neural network formation. Both gamma-aminobutyric acid (GABA) receptors and N-methyl-D-aspartate (NMDA) ionotropic glutamate receptors are targets of commonly used anaesthetic agents – such agents could potentially be neurotoxic and cause neurodevelopmental disturbances. Even though in vitro and animal experimental data show neurotoxic effects, clinical evidence in humans is still lacking. Due to the heterogeneity of study designs and extensive confounding, it is difficult to draw solid conclusions. Therefore, in this review we discuss brain development, the role of glutamate and GABA, effects of modulating GABAa and NMDA receptors in the developing brain and current prospects of clinical trials.

Keywords: brain development; anesthesia; gamma-aminobutyric acid; N-metil-D-aspartate receptor.