Extracellular Vesicle Levels of Nervous System Injury Biomarkers in Critically Ill Trauma Patients with and without Traumatic Brain Injury
Open accessAbstract
Moderate/severe traumatic brain injury (TBI) causes injury patterns with heterogeneous pathology producing varying outcomes for recovery. Extracellular vesicles (EVs) are particles containing a myriad of molecules involved in cell signaling. EVs may hold promise as biomarkers in TBI because of their encapsulation, including improved stability/decreased degradation. A subset of subjects with and without TBI from a prospective, observational trial of critically ill trauma patients were analyzed. Total EV levels of glial (glial fibrillary acidic protein; GFAP) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 [UCH-L1], neurofilament light chain [NfL], and total-tau) proteins were measured using single-molecule array technology. Protein levels were winsorized to address outliers and log transformed for analysis. Patients with multiple injuries ( n = 41) and isolated body injury ( n = 73) were of similar age and sex. Patients with multiple injuries were, as expected, more severely injured with higher Injury Severity Scores (29 [26–41] vs. 21 [14–26], p < 0.001) and lower Glasgow Coma Scale scores (12 [4–13] vs. 13 [13–13], p < 0.001). Total body EVs of GFAP, UCH-L1, and NfL were higher in those with multiple injuries (1768 [932–4780] vs. 239 [63–589], p < 0.001; 75.4 [47.8–158.3] vs. 41.5 [21.5–67.1], p = 0.03; 7.5 [3.3–12.3] vs. 2.9 [2.1–4.8], p < 0.001, respectively). There was a moderate correlation between the Head Abbreviated Injury Score and GFAP (free circulating rho = 0.62, EV rho = 0.64; both p < 0.001). Brain-derived proteins contained in EV holds promise as an informative approach to biomarker measurement after TBI in hospitalized patients. Future evaluation and longitudinal studies are necessary to draw conclusions regarding the clinical utility of these biomarkers.
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Efforts to identify EV-based biomarkers for TBI have largely centered on well-characterized proteins like UCHL1, Tau, and Aβ.
“Efforts to identify EV-based biomarkers for TBI have largely centered on well-characterized proteins like UCHL1, Tau, and Aβ [184–186].”
From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [186]
The Methods report measuring EV-associated UCH-L1 and tau, and the Discussion describes a prior study of EV amyloid-beta 42 in mild TBI. The paper therefore supports these proteins as examples of EV biomarkers studied in TBI, but it does not establish that efforts in the field have largely centered on them; its own study also measures GFAP and NfL. The indexed passages provide section labels but no page numbers. (LLM, conf=0.81)
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- Authors
- Guedes, V. A., Mithani, S., Williams, C., Sass, D., Smith, E. G., Vorn, R., Wagner, C., Lai, C., Gill, J., & Hinson, H. E.
- Affiliations
- National Institutes of Health (US)
- The University of Texas at San Antonio Health Science Center (US)
- Oregon Health & Science University (US)
- Johns Hopkins University (US)
- Corresponding author
- Hinson, Holly E.
- ORCID
- Venue
- Neurotrauma Reports
- Publisher
- SAGE Publications
- Published
- 2022-09-01
- Volume
- 3
- Issue
- 1
- Pages
- 545-553
- ISSN
- 2689-288X (ISSN-L)
- PMC
- PMC9811954
- OpenAlex
- W4313418258
- Cited by
- 15
- References
- 29
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 4 · 2023: 3
- FWCI
- 1.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neurotrauma Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K23HL150229)
- National Institute of Neurological Disorders and Stroke (K23NS110828)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, extracellular vesicles, neuroinflammation biomarkers, glial fibrillary acidic protein, UCHL1, neurofilament light chain, tau protein, polytrauma, critically ill trauma patients, injury severity, single molecule array
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