Elevation of protective autophagy as a potential way for preventing developmental neurotoxicity of general anesthetics

Numerous animal studies have demonstrated that commonly used general anesthetics could cause cognitive impairment in the developing brain. However, the underlying mechanism remains unclear. Recently it is reported that autophagy activation can ameliorate developmental neurotoxicity of ethanol, which is the same GABAA agonist and NMDA antagonist as general anesthetics. We thus intend to propose the possible role of autophagy in the developmental neurotoxicity of general anesthetics. Oxidative stress and neuronal apoptosis can activate autophagy, while autophagy conversely alleviates their levels in the neuron. Crosstalk among neuronal apoptosis, oxidative stress and autophagy resembles the Yin-Yang relationship in Chinese philosophy. Neuronal apoptosis and oxidative stress represent destroyable Yin, while autophagy symbols protective Yang. The destroyable Yin and protective Yang promote and counteract each other. We hypothesize that the destroyable Yin (neuronal apoptosis and oxidative stress injury) prevails over protective Yang (autophagy) when developing brain exposes to general anesthetics. Elevating protective Yang autophagy potentially reverses the neurotoxicity of general anesthetics. Once this hypothesis is proved, it will provide a new perspective to understand the developmental neurotoxicity of general anesthetics and a new way to prevent it.