Cellular Mechanisms Associated with Neurodevelopmental Alterations Produced by General Anesthetics

Abstract

: There is concern about neurodevelopmental disturbances associated with exposure to general anesthesia during early childhood. In 2016, the U.S. Food and Drug Administration released a safety alert regarding the use of gamma-aminobutyric acid (GABA) agonists and N-methyl-D-aspartate (NMDA) receptor antagonists in pediatric anesthesia, warning about the risks of their use during the last trimester of pregnancy and in children under 3 years for neurodevelopment. Animal and in vitro studies demonstrate worrisome morphological and functional alterations in young neurons and glia induced by different anesthetic drugs. These drugs can induce changes in various neuronal transmission systems, alter dendritic growth and brain connectivity, and initiate processes leading to cell demise, such as aberrant cell cycle reentry, mitochondrial dysfunction, excitotoxicity, neuroapoptosis, disruption of cytoskeletal assembly, and dysregulation of brain-derived neurotrophic factor (BNDF). Additionally, they can generate epigenetic changes that can be transmitted intergenerationally. These effects are related to age, dose, number of anesthetics received, and duration of exposure to said drugs and can be reversible or permanent, caused by direct or indirect perturbations on neurons. These disturbances may manifest as neurodevelopmental disorders later in life. This work aimed to review the cellular mechanisms involved in these alterations.