Broad-Coverage Lipidomics Reveals Temporal Lipid Remodeling and Candidate Serum Biomarkers After Acute Spinal Cord...

Objective: To systematically characterize temporal lipid metabolic remodeling in serum and spinal cord tissue following spinal cord injury (SCI) and to identify candidate serum lipid biomarkers associated with disease progression. Methods: A moderate-to-severe SCI model was established in Sprague-Dawley rats using a modified MASCIS weight-drop contusion protocol. Serum and injured spinal cord tissue were collected at 6 h, 1 d, 3 d, 7 d, and 14 d after injury. Broad-coverage lipidomic profiling was performed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In parallel, transcriptomic profiling of injured spinal cord tissue was conducted, followed by bioinformatic analyses and RT-qPCR validation of selected metabolic genes. Results: Broad-coverage lipidomic analysis showed significant and dynamic lipid remodeling in both serum and spinal cord tissue after SCI. The serum lipid profile exhibited a multiphasic pattern, with early suppression, intermediate activation, and late-stage remodeling. Structural phospholipid subclasses showed coordinated temporal changes after injury. Long-chain acylcarnitines (LCACs) increased rapidly in serum during the acute phase and then gradually accumulated in the injured spinal cord tissue. In contrast, cholesteryl esters (CEs) progressively accumulated in spinal cord tissue, while showing a biphasic pattern in serum, with an early decrease followed by a rebound increase. Receiver operating characteristic curve analysis showed that LCACs and CEs had excellent discriminatory performance across multiple post-injury stages. Conclusions: SCI is associated with extensive lipid metabolic reprogramming in both serum and spinal cord tissue. LCACs and CEs represent promising candidate serum biomarkers closely associated with disease progression. Multi-omics analyses further suggest that serum lipid remodeling parallels lipid metabolic and inflammatory reprogramming in the injured spinal cord, while the contribution of local pathology to circulating LCAC and CE changes remains to be clarified.