Isoflurane impairs the capacity of astrocytes to support neuronal development in a mouse dissociated coculture model

Background: There is growing concern that pediatric exposure to anesthetic agents may cause long-lasting deficits in learning by impairing brain development. Most studies to date on this topic have focused on the direct effects of anesthetics on developing neurons. Relatively little attention has been paid to possible effects of anesthetics on astrocytes, a glial cell type that plays an important supporting role in neuronal development. Methods: Astrocytes were exposed to isoflurane and then cocultured with unexposed neurons to test for astrocyte-specific toxic effects on neuronal growth. Axon length was measured in the cocultured neurons to assess neuronal growth. Results: We found that neurons cocultured with astrocytes exposed to isoflurane exhibited a 30% reduction in axon outgrowth. Further experimentation showed that this effect is likely due to reduced levels of brain-derived neurotrophic factor in the coculture media. Conclusions: Isoflurane interferes with the ability of cultured astrocytes to support neuronal growth. This finding represents a potentially novel mechanism through which general anesthetics may interfere with brain development.