Remote blast-related mild traumatic brain injury is associated with differential expression of exosomal microRNAs identified in neurodegenerative and immunological processes

Christina Devoto, Vivian A. Guedes, Chen Lai, Jacqueline J. Leete, Sara Mithani, Katie Edwards, Rany Vorn, Bao Xi Qu, Elisabeth A. Wilde, William C. Walker, Ramon Diaz-Arrastia, J. Kent Werner, Kimbra Kenney, Jessica M. Gill

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Blast traumatic brain injury (TBI) and subconcussive blast exposure have been associated, pathologically, with chronic traumatic encephalopathy (CTE) and, clinically, with cognitive and affective symptoms, but the underlying pathomechanisms of these associations are not well understood. We hypothesized that exosomal microRNA (miRNA) expression, and their relation to neurobehavioral outcomes among Veterans with blunt or blast mild TBI (mTBI) may provide insight into possible mechanisms for these associations and therapeutic targets. Methods: This is a subanalysis of a larger Chronic Effects of Neurotrauma Consortium Biomarker Discovery Project. Participants (n = 152) were divided into three groups: Controls (n = 35); Blunt mTBI only (n = 54); and Blast/blast+blunt mTBI (n = 63). Postconcussive and post-traumatic stress symptoms were evaluated using the NSI and PCL-5, respectively. Exosomal levels of 798 miRNA expression were measured. Results: In the blast mTBI group, 23 differentially regulated miRNAs were observed compared to the blunt mTBI group and 23 compared to controls. From the pathway analysis, significantly dysregulated miRNAs in the blast exposure group correlated with inflammatory, neurodegenerative, and androgen receptor pathways. Discussion: Our findings suggest that chronic neurobehavioral symptoms after blast TBI may pathomechanistically relate to dysregulated cellular pathways involved with neurodegeneration, inflammation, and central hormonal regulation.

Original languageEnglish (US)
Pages (from-to)652-661
Number of pages10
JournalBrain Injury
Volume36
Issue number5
DOIs
StatePublished - 2022
Externally publishedYes

Keywords

  • Blast
  • military
  • neurological symptoms

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Developmental and Educational Psychology
  • Clinical Neurology

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