Lipid droplets as redox-active organelles after spinal cord injury: lipid peroxidation, mitochondrial dysfunction, and neuroinflammation
Abstract
Abstract Objectives Spinal cord injury (SCI) causes myelin breakdown and membrane disruption, leading to the release and redistribution of cholesterol, fatty acids, and other lipids within the lesion. The resulting disruption of lipid homeostasis can promote sustained lipid peroxidation, neuroinflammation, and repair failure. In recent years, lipid droplets (LDs) have been recognized as highly dynamic organelles that coordinate lipid storage, mobilization, energy metabolism, and stress responses. However, the stage- and cell-specific roles of LDs in lipid–redox dysregulation after SCI remain poorly understood. Methods This review summarizes the basic mechanisms of LD formation, lipolysis, and lipophagy, examines the regulation of lipid peroxidation by LDs, and discusses bidirectional LD–mitochondria crosstalk. We further integrate evidence on LD remodeling across microglia/macrophages, astrocytes, neurons, oligodendrocyte-lineage cells, and microvascular endothelial cells. We also consider how these cell-specific changes relate to lipid detoxification and transfer, neuronal oxidative injury, blood–spinal cord barrier dysfunction, and remyelination. Results We propose that LDs are not passive markers of lipid deposition after SCI but stage- and cell-type-dependent redox–metabolic regulators. Early LD formation may buffer acute lipid overload, whereas persistent oxidative stress, mitochondrial dysfunction, and impaired LD turnover may convert LDs into pathological lipid reservoirs that amplify lipid peroxidation and neuroinflammation. Finally, we discuss therapeutic strategies aimed at limiting pathological lipid accumulation, restoring LD turnover and cholesterol efflux, suppressing lipid peroxidation, and preserving mitochondrial redox homeostasis. Discussion Together, this review provides an integrated framework for understanding how LD remodeling links lipid metabolic imbalance to secondary injury and neural repair after SCI.