Background: Ethanol is known to have both γ-Aminobutyric acid agonist and Nmethyl-
D-aspartate antagonist characteristics similar to commonly used volatile anesthetic
agents. Recent evidence demonstrates that autophagy can reduce the development of ethanol
induced neurotoxicity. Recent studies have found that general anesthesia can cause longterm
impairment of both mitochondrial morphogenesis and synaptic transmission in the developing
rat brain, both of which are accompanied by enhanced autophagy activity. Autophagy
may play an important role in general anesthetic mediated neurotoxicity.
Methods: This review outlines the role of autophagy in the development of anesthetic related
neurotoxicity and includes an explanation of the role of autophagy in neuronal cell
survival and death, the relationship between anesthetic agents and neuronal autophagy, possible
molecular and cellular mechanisms underlying general anesthetic agent induced activation
of neuronal autophagy in the developing brain, and potential therapeutic approaches
aimed at modulating autophagic pathways.
Results: In a time- and concentration-dependent pattern, general anesthetic agents can disrupt
intracellular calcium homeostasis which enhances both autophagy and apoptosis activation.
The degree of neural cell injury may be ultimately determined by the interplay between
autophagy and apoptosis. It appears likely that the increase in calcium flux associated with
some anesthetic agents disrupts lysosomal function. This results in an over-activation of endosomal-
lysosomal trafficking causing mitochondrial damage, reactive oxygen species upregulation,
and lipid peroxidation.
Conclusion: Autophagy may play a role in the development of anesthetic related neurotoxicity.
Understanding this may lead to strategies or therapies aimed at preventing or ameliorating
general anesthetic agent mediated neurotoxicity.