Exposure of young animals to most clinically-utilized anesthetics in sufficient doses changes brain structure and affects cognition and behavior in later life. The question of whether these findings can be translated to children has spurred numerous studies, reviews of these studies, and commentaries. In the current issue, two of the leading investigators in this field provide an excellent critical review of the literature about children, including recent studies that have contributed significantly to our understanding. As rightly noted by the review authors, the concerns about whether anesthetics may be “neurotoxic” in children, and indeed the Food and Drug Administration’s warning about the potential neurotoxic effects of most anesthetics, were driven primarily by observations in animals, not by an “obvious clinical problem.” Concerns about adverse neurodevelopmental outcomes after major neonatal and cardiac surgery are longstanding, but any such effects were typically attributed to the underlying conditions necessitating surgery and other perioperative factors, rather than anesthesia, per se. The potential for relatively short-term postoperative changes in behavior is well recognized, but few suspected that anesthesia itself could have long-term neurodevelopmental effects. This lack of suspicion has been used to argue against any significant effects of anesthesia exposure, as surely if this was a real problem, then we would have noticed it by now. Why have we not, other than the possibility that there is no problem?
- Z-DNA/RNA Binding Protein 1 Senses Mitochondrial DNA to Induce Receptor-Interacting Protein Kinase-3/Mixed Lineage Kinase Domain-Like-Driven Necroptosis in Developmental Sevoflurane Neurotoxicity.
- Embryonic exposure to fentanyl induces behavioral changes and neurotoxicity in zebrafish larvae.
- Sevoflurane induces neurotoxic effects on developing neurons through the WNK1/NKCC1/Ca2+ /Drp-1 signalling pathway.
- Single-nucleus atlas of sevoflurane-induced hippocampal cell-type- and sex-specific effects during development in mice.
- Ketamine impairs growth cone and synaptogenesis in human GABAergic projection neurons via GSK-3β and HDAC6 signaling.