Circulating microRNA Profiles in Acute Spinal Cord Injury: Evidence for Distinct Plasma Signatures Compared with Polytrauma Patients
Background: Traumatic spinal cord injury (SCI) is a devastating complication of trauma, causing long-term disability and significant socioeconomic burden. Beyond the primary mechanical insult, secondary injury cascades involving apoptosis, oxidative stress, and inflammation amplify tissue damage. MicroRNAs (miRNAs) regulate these processes at the post-transcriptional level, yet data on circulating miRNAs in human SCI remain scarce. Objective: This study aimed to characterize acute plasma miRNA expression patterns in isolated SCI that may indicate SCI-specific signatures. Methods: Plasma was collected from five SCI patients at admission and 48 h post-injury and five healthy controls (HC) and Next-generation sequencing (NGS) was performed on plasma RNAs. Differentially expressed miRNAs were identified and selected candidate miRNAs were validated by droplet digital PCR (ddPCR) in an expanded cohort of SCI patients, polytrauma patients without neurotrauma (PT), and HC (each n=8). Pathway enrichment and validated target analysis were performed to assess biological relevance of candidate miRNAs. Results: At emergency room admission, 46 miRNAs were differentially expressed in SCI plasma (18 upregulated, 28 downregulated). By 48 h, a global downregulation was observed, with 47 miRNAs significantly decreased compared with HC. ddPCR validation revealed markedly stronger suppression of miR-182-5p, miR-190a-5p, miR-144-5p, and miR-30c-5p expression levels in SCI compared with PT, suggesting a neurogenic rather than trauma-related regulation. Pathway analysis indicated enrichment of mitochondrial oxidative phosphorylation pathways, and target prediction suggested that the identified miRNAs may be linked to neuroprotective and regenerative functions. Conclusion: Our findings demonstrate early and profound alterations in circulating miRNAs after acute SCI. The downregulation of the identified miRNAs may reflect maladaptive changes that promote neuroinflammation and hinder axonal regeneration, although the exact functional consequences remain to be clarified. These data suggest that circulating miRNAs could hold promise as diagnostic and prognostic biomarkers and, potentially, as therapeutic targets to influence secondary injury processes. Overall design: RNA-seq profiling of plasma from trauma patients with isolated spinal cord injury, collected at emergency room admission and 48 hours after trauma, compared with healthy controls.