METABOLOMIC AND PROTEOMIC PROFILING REVEAL RECOVERY-RELATED SERUM SIGNATURES IN SPINAL CORD INJURY PATIENTS UNDER REHABILITATION

Spinal cord injury (SCI) is an untreatable neuropathology impairing motor, sensory, and autonomic functions. Given the CSF-blood interconnection and SCI systemic impacts, circulating biomarkers are worth exploring. Aiming to identify recovery-related serum molecular signatures, a longitudinally-controlled study (NCT07383077) monitored the serum metabolites and proteins of SCI patients’ pre- and post-rehabilitation (n=66), and 1-year post-injury (n=55), against 40 age-/sex-matched controls. Attenuated Total Reflection Fourier-transform infrared (ATR-FTIR) spectroscopy revealed a SCI signature of fatty acids alterations, disordered protein conformations, and shifts in carbohydrates, nucleic acids, and lactate. Injury severity could be discriminated, with less severe SCI patients resembling controls. Rehabilitation partially normalized the serum metabolome, with some changes persisting until 1-year post-injury. Various spectral peaks were consistently linked to opposite health statuses. Concurrently, mass-spectrometry characterized the undepleted serum proteome of a cohort subgroup (n=30 patients and controls). SCI downregulated lipid transport and metabolism-related proteins and upregulated innate immune pathways, mainly complement. Again, rehabilitation partially reverted alterations: immune-related processes attenuated, lipid metabolism increased. Tissue growth/repair proteins were also deregulated. About half of SCI-upregulated proteins decreased with rehabilitation and negatively correlated with recovery measures, while half of rehabilitation-induced proteins (previously decreased by SCI) were positively correlated. Incubation of human iPSC-derived neurons with 'best' and 'worst' post-rehabilitation sera affected differentiation and apoptosis. This study highlights ATR-FTIR as a high-throughput, label-free tool for SCI stratification and metabolomic monitoring, and reveals that rehabilitation partially normalizes SCI-induced metabolome and proteome alterations. The recovery-related molecules and pathways here identified support future SCI targeted therapies.