Anesthesia-induced neurotoxicity in an animal model of the developing brain: mechanism and therapies.

Abstract

Children are being exposed to an increasingly greater variety of anesthetics with advances in pediatric and obstetric surgery. Recent animal and retrospective human data suggest that the general anesthetics commonly used in pediatric medicine could be damaging to the developing brain when used at clinical concentrations. In vivo primate and rodent models have shown that neonatal exposure to clinical concentrations of anesthetics causes neural apoptosis and long-term cognitive impairment. Many general anesthetics, such as isoflurane, sevoflurane, barbiturates, benzodiazepines, ketamine, propofol, and nitrous oxide, cause adverse changes in the neonatal rodent and primate brain. Animal and human data suggest an association between general anesthesia during the neonatal period and long-term cognitive impairment. Cohort studies involving humans have recently been started. The window of vulnerability to these neurotoxic effects of anesthetics is restricted to the period of synaptogenesis, also known as the “brain growth spurt” (BGS) period. To minimize the risk of neurodegeneration, it is necessary to study both the mechanism of neurotoxicity and preventative medicine. Neonatal anesthetic exposure affects many mechanisms of neurotoxicity. Mechanisms of anesthetic-induced neurotoxicity seem to involve altered expression of ligand-gated ion channels, disturbance of intracellular calcium homeostasis, and the mitochondria-mediated apoptotic pathway. Several agents reportedly help to prevent anesthesia-induced neurotoxicity, including hydrogen, melatonin, apocynin, and ketorolac, and should thus be co-administered with anesthetics. After anesthesia, only environmental enrichment can improve learning deficits due to anesthesia-induced neurotoxicity. Further studies of environmental enrichment (Wu et al., 2016) after anesthesia are necessary to develop preventative and therapeutic strategies for anesthesia-induced neurotoxicity.