Introduction: Acute traumatic spinal cord injury (aSCI) is a heterogenous condition that currently lacks reliable diagnostic and prognostic biomarkers to guide clinical care. CSF biomarkers that classify injury severity and predict recovery are actively being investigated. Exosomes are small membrane derived vesicles that participate in cell-to-cell transfer of proteins, serving as critical mediators after aSCI. In this study, we characterize the CSF exosome proteome of aSCI patients and evaluate their ability to predict injury severity and neurologic recovery.
Methods: CSF samples were obtained from prospectively enrolled patients with aSCI through a lumbar intrathecal catheter on days 1-5 postinjury. Exosomes were extracted from CSF and lysed to isolate the protein content. Proteins were characterized through multiplex ELISA studies using a 30-plex human cytokine panel. Differential expression analysis was performed on Limma. Neurologic impairment was defined by the ASIA Impairment Scale (AIS) grade at presentation and 3 months postinjury.
Results: Twenty-seven aSCI patients (12 AIS A, 8 AIS B, and 7 AIS C) were included in the study. The levels of glial fibrillary acidic protein (GFAP), amyloid beta 1-42, RANTES and GM-CSF were significantly elevated in baseline AIS A patients. Neurologic improvement was seen in 66.7% of all patients at 3 months follow up. The levels of interleukin (IL)-10, chemokine ligand (CCL)-11 and macrophage inflammatory protein (MIP)-1 beta were significantly higher in patients that had AIS grade conversion.
Conclusion : This is the first study characterizing CSF exosomal protein contents, which provide valuable information for clinical management and evaluation of novel SCI therapies. Proteomic analysis showed differential concentrations of CSF exosome proteins based on aSCI injury severity and predicted short-term outcomes.
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