Every year, a large number of human fetuses and infants receive anesthesia worldwide, and perioperative mortality and morbidity is several folds higher in these populations compared with older children. Anesthetics interfere with GABAergic and glutamatergic neurotransmissions that play a critical role in brain development. In this context, our main research interest is to elucidate whether anesthetics, as potent pharmacological modulators of GABAergic and glutamatergic signaling, interfere with central nervous system (CNS) development.
Recent observations in our laboratory suggest that anesthetics could induce long-term alterations in dendritic development of cultured neurons. Given that dendrites represent the primary sites of synaptic contacts in neurons and are major determinants of a neuron's electrophysiological properties, these results raise the possibility that exposure of developing neurons to anesthetics could seriously impair neuronal network formation. If confirmed, this would have extremely important clinical implications in pediatric anesthesia practice, since the most intense phase of dendritic differentiation and synaptogenesis takes place during the last trimester of pregnancy and the first few years of postnatal life.
Therefore, a key issue is to determine whether anesthesia could lead to altered development of dendritic arbors and neuronal networks in vivo. In our current research projects, we address this issue by taking advantage of a combination of in vivo single cell labeling and tracing methodologies that were recently developed in our research group. We also attempt to elucidate the molecular mechanisms underlying anesthetics-induced adverse effects on neuronal development during the early postnatal period. In this context, special emphasis is placed on studying how anesthetics might affect physiological aspects of neurotransmission mediated by the GABAA receptor during the peak synaptogenic period. For these purposes, we use a combination of electrophysiological, biochemical, morphological and functional techniques.
Results of this project would represent a significant advancement in our understanding about the potential adverse effects of anesthetics on CNS development. This is an important step towards developing new strategies to prevent adverse effects of anesthesia on the immature brain.