Plasma extracellular vesicles as a source of biomarkers in traumatic brain injury

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  • 1 Departments of Neurological Surgery and
  • 2 Immunology, Mayo Clinic, Rochester;
  • 3 Mayo Clinic Graduate School of Biomedical Sciences, Rochester, Minnesota; and
  • 4 Department of Neurosurgery, University of Pittsburgh, Pennsylvania
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OBJECTIVE

The objective of this study was to isolate extracellular vesicles (EVs) from plasma in a cohort of patients with traumatic brain injury (TBI) and analyze their contents for novel biomarkers that could prove useful for rapid diagnosis and classification of brain injury during initial evaluation.

METHODS

Plasma EVs were isolated by serial ultracentrifugation from patients with TBI (n = 15) and healthy controls (n = 5). Samples were obtained from the TRACK-TBI biorepository (2010–present). Size and concentration were determined by nanoparticle tracking. Glial fibrillary acidic protein (GFAP) concentration was determined in EV protein. EV RNA was isolated and deep sequencing of short noncoding RNA was performed.

RESULTS

Plasma EVs are physically similar but contained approximately 10 times more GFAP in TBI patients with altered consciousness than patients and controls with normal consciousness. Eleven highly differentially expressed microRNAs (miRNAs) were identified between these groups. Genes targeted by these miRNAs are highly associated with biologically relevant cellular pathways, including organismal injury, cellular development, and organismal development. Multiple additional coding and noncoding RNA species with potential biomarker utility were identified.

CONCLUSIONS

Isolating plasma EVs in patients with TBI is feasible. Increased GFAP concentration—a validated plasma TBI marker—in EVs from TBI patients with altered consciousness, along with differential expression of multiple miRNAs targeting TBI-relevant pathways, suggests that EVs may be a useful source of TBI biomarkers. Additional evaluation in larger patient cohorts is indicated.

ABBREVIATIONS EV = extracellular vesicle; GCS = Glasgow Coma Scale; GFAP = glial fibrillary acidic protein; lincRNA = long intervening noncoding RNA; miRNA = microRNA; mRNA = messenger RNA; rRNA = ribosomal RNA; snoRNA = small nucleolar RNA; snRNA = small nuclear RNA; TBI = traumatic brain injury; TRACK-TBI = Transforming Research and Clinical Knowledge in Traumatic Brain Injury; UCH-L1 = ubiquitin carboxy-terminal hydrolase L1.

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Contributor Notes

Correspondence Ian F. Parney: Mayo Clinic, Rochester, MN. parney.ian@mayo.edu.

INCLUDE WHEN CITING Published online July 24, 2020; DOI: 10.3171/2020.4.JNS20305.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

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