Cerebrospinal fluid extracellular vesicle-derived miR-9-3p in spinal cord injury with neuroprotective implications and biomarker development.

Spinal cord injury (SCI) often results in severe disability, and early detection of molecular changes is crucial for guiding treatment. In both rat and human samples, we observed a significant increase in cerebrospinal fluid (CSF)-derived extracellular vesicle (EV) miR-9-3p after SCI, prompting further investigation into its role. In a rat model, miR-9-3p levels were significantly lower at the injured spinal levels but higher in the motor cortex, where astrocytes showed the highest expression. Functional analyses revealed that miR-9-3p regulates energy metabolism, immune activity, and oxidative stress in neurons, inducing transcriptional changes suggestive of stress adaptation and synaptic remodeling. These findings demonstrate that EV-associated miR-9-3p modulates injury responses by reducing energy demands and supporting structural and functional adaptation, establishing it as a promising biomarker and therapeutic target for acute SCI.