Biomed Res Int. 2016;2016:7919640. doi: 10.1155/2016/7919640. Epub 2016 Feb 1.
Demand is increasing for safer inhalational anesthetics for use in pediatric anesthesia. In this regard, researchers have debated whether isoflurane is more toxic to the developing brain than desflurane. In the present study, we compared the effects of postnatal exposure to isoflurane with those of desflurane on long-term cognitive performance and investigated the role of the Akt/GSK3β signaling pathway. Postnatal day 6 (P6) mice were exposed to either isoflurane or desflurane, after which the phosphorylation levels of Akt/GSK3β and learning and memory were assessed at P8 or P31. The phosphorylation levels of Akt/GSK3β and learning and memory were examined after intervention with lithium. We found that isoflurane, but not desflurane, impaired spatial learning and memory at P31. Accompanied by behavioral change, only isoflurane decreased p-Akt (ser473) and p-GSK3β (ser9) expressions, which led to GSK3β overactivation. Lithium prevented GSK3β overactivation and alleviated isoflurane-induced cognitive deficits. These results suggest that isoflurane is more likely to induce developmental neurotoxicity than desflurane in context of multiple exposures and that the Akt/GSK3β signaling pathway partly participates in this process. GSK3β inhibition might be an effective way to protect against developmental neurotoxicity.
Nowadays, the administration of most of the anesthetics is being questioned. The quality of reversibility of these medications is being questioned, especially when administered to children under 3 years old. The administration of isoflurane elevates intracellular calcium levels which are critical for cell damage resulting in apoptosis. The NMDA and GABA receptors are indirectly involved in the effect of immature brains. The immaturity of the central nervous system associated to the administration of anesthetic agents such as inhaled anesthetics, ketamine, midazolam, nitrous oxide, and others, produces important changes in the brain that have an impact in the child's later life. There are two important elements in the neurotoxicity of anesthetics, dosage and time administration. Repeating anesthetics produces more brain changes. These modifications have resulted in serious behavioral and memory changes in experiments in animals. It is suspected that a similar situation may arise in children who manifest learning disabilities in later stages.