Extracellular Vesicle-Based Biomarkers in Spinal Cord Injury: A State-of-the-Art Review on Diagnostic and Prognostic...

Spinal cord injury (SCI) is a devastating neurological disorder that can result in permanent disability and reduced quality of life, characterized by heterogeneous injury mechanisms and limited tools for accurate early diagnosis and prognostic stratification. The clinical course of SCI is driven not only by the initial mechanical insult but also by complex secondary injury cascades involving neuroinflammation, axonal degeneration, demyelination, and maladaptive repair responses. Current diagnostic and prognostic approaches, which rely largely on neurological examination and imaging, provide limited insight into these dynamic molecular processes. In this context, extracellular vesicles (EVs) have emerged as a biologically compelling source of biomarkers for SCI. EVs are released by neurons, glial cells, endothelial cells, and immune cells and carry molecular cargo that reflects cellular stress, injury severity, and endogenous repair activity. Increasing evidence indicates that EV-associated proteins and regulatory microRNAs (miRNAs) encode injury-specific signatures related to neuronal and glial damage, inflammatory signaling, metabolic stress, and functional recovery potential. In this review, we summarize the current knowledge on EV biology in SCI and discuss emerging evidence supporting EV-derived proteins and miRNAs as promising tools for refining diagnosis and prognosis. Our aim is not only to consolidate established findings but also to highlight EV-based molecular signatures as a developing framework for precision biomarker discovery in SCI.