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10.1172/jci.insight.205134
1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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1The Department of Neurosurgery, The University of Texas Health Science Center, Houston, United States of America
2Carolina Neurosurgery and Spine Associates, Charlotte, United States of America
3Division of Clinical and Translational Sciences, The University of Texas McGovern Medical School, Houston, United States of America
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Published June 23, 2026 - More info
Spinal cord injury (SCI) leads to severe neurological and functional impairments, yet reliable biomarkers for assessing injury severity and predicting recovery remain limited. Cerebrospinal fluid (CSF) is in direct contact with the central nervous system and provides a valuable source for detecting molecular changes after SCI. Although exosomal microRNAs and proteins are increasingly recognized as mediators of intercellular communication, the role of human CSF exosomes in SCI has not been systematically investigated. To identify exosome-based biomarkers and potential therapeutic targets, we analyzed CSF and serum exosomes from patients with acute SCI using RNA sequencing and proteomic profiling. Weighted Gene Co-expression Network Analysis (WGCNA) identified six gene modules significantly associated with injury severity and neurological recovery at three months. Proteomic analysis revealed a five-protein panel that distinguished complete from incomplete SCI and a four-protein panel that predicted neurological improvement. Additionally, fifteen CSF-specific and nine serum-specific exosomal miRNAs were identified independent of injury severity. Among ten tested miRNAs associated with neurological recovery, seven regulated astrocyte proliferation, and six promoted neurite extension and synapse formation. Overall, this study provides a comprehensive characterization of CSF exosomal miRNAs and proteins in human SCI and identifies molecular signatures associated with injury severity and recovery.