Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.

Abstract

Anesthetics are indispensable in clinical practice, yet growing evidence indicates that they can disrupt brain function beyond their intended effects. While research on anesthetic neurotoxicity has largely focused on neurons, microglia are now recognized as central players in determining perioperative outcomes. Lipid metabolism in microglia has emerged as a key regulator of immune responses, synaptic maintenance, and neuroinflammation. Anesthetic exposure disturbs this metabolic balance, leading to lipid droplet accumulation, defective fatty acid oxidation, and pro-inflammatory activation that contribute to cognitive impairment. However, knowledge in this field remains fragmented and has not been systematically synthesized. In this review, we integrate current evidence on how anesthetics perturb microglial lipid metabolism and delineate the mechanistic pathways involved, with the goal of identifying potential therapeutic targets related to microglial lipid metabolism to alleviate anesthesia neurotoxicity.