Context-Dependent Roles of Four Classes of Bioactive Lipids in Neuroglia-Mediated Regulation of Neuroinflammation

Neuroinflammation is an adaptive immune response of the nervous system to tissue injury or microbial invasion. As innate immune cells of the central nervous system, neuroglia cells-especially astrocytes and microglia-play a critical role in maintaining neural homeostasis. Bioactive lipids, key molecules at the core of tissue immune homeostasis, regulate a variety of biological activities with precision, participating in the management of neuroinflammation, a process often mediated by glial cells. The four major classes of bioactive lipids, including classic eicosanoids, specialized pro-resolving mediators (SPMs), endocannabinoids (eCBs), and lysophospholipids/sphingolipids (LPLs/SPs), influence the regulation of neuroinflammation in a context-dependent manner by affecting the phenotypic changes and activation states of neuroglial cells, thus collectively contributing to the modulation of neuroinflammation. A comprehensive review and summary of these regulatory mechanisms will provide potential directions for future research integrating emerging single-cell lipidomics techniques and clinical trials of lipid-based therapeutics. In-depth exploration of this field holds great promise for offering novel strategies for the early diagnosis and treatment of neurological disorders.