Genetic Assessment of Neurotoxicity Accompanied by Inhalational Anesthesia in Preclinical Studies with Focus on Sevoflurane and Isoflurane—A Narrative Review

Inhalational anesthesia, which includes anesthetics such as sevoflurane, isoflurane, and desflurane, is widely used in clinical settings for surgical interventions across all age groups. Nonetheless, recent findings from preclinical research raise important questions regarding their potential neurotoxic effects, especially within the developing brain, though clinical implications remain to be fully established. This narrative review was conducted through a literature search of the PubMed database and synthesizes preclinical investigations into gene modifications associated with neurotoxicity following exposure to inhalation anesthetics. Emphasis was placed on anesthetic exposure in human and animal-derived cell lines, neurodevelopmental animal models, as well as adult and aged animals. In various models, the neurotoxic mechanisms of inhalational anesthesia involve a complex interaction of apoptosis, oxidative stress, mitochondrial dysfunction, neuroinflammation, and epigenetic remodeling. Developmental studies indicate additional susceptibilities, including impaired neuronal migration, myelination deficits, and transgenerational epigenetic effects, whereas aging models exhibit oxidative stress injury, microglial activation, and heightened perioperative neurocognitive sensitivity. Understanding these neurotoxic mechanisms is essential for identifying risk factors, formulating age-specific neuroprotective strategies, and enhancing the overall safety of anesthetic use, particularly in vulnerable populations.