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Review
. 2022 Feb 10:12:698206.
doi: 10.3389/fneur.2021.698206. eCollection 2021.

Developing Biomarkers of Mild Traumatic Brain Injury: Promise and Progress of CNS-Derived Exosomes

Melonie N Vaughn  1 , Charisse N Winston  1 , Natalie Levin  1 , Robert A Rissman  1   2 , Victoria B Risbrough  2   3   4
Affiliations
Review

Developing Biomarkers of Mild Traumatic Brain Injury: Promise and Progress of CNS-Derived Exosomes

Melonie N Vaughn et al. Front Neurol. .

Abstract

Mild traumatic brain injuries (mTBI) are common injuries across civilian and military populations. Although most individuals recover after mTBI, some individuals continue to show long-term symptoms as well as increased risk for neurodegenerative and neuropsychiatric disorders. Currently, diagnosing TBI severity relies primarily on self-report and subjective symptoms, with limited tools for diagnosis or prognosis. Brain-derived exosomes, a form of extracellular vesicle, may offer a solution for interpreting injury states by aiding in diagnosis as well as outcome prediction with relatively low patient burden. Exosomes, which are released into circulation, contain both protein and RNA cargo that can be isolated and quantified, providing a molecular window into molecular status of the exosome source. Here we examined the current literature studying the utility of exosomes, in particular neuronal- and astrocyte-derived exosomes, to identify protein and miRNA biomarkers of injury severity, trajectory, and functional outcome. Current evidence supports the potential for these emerging new tools to capture an accessible molecular window into the brain as it responds to a traumatic injury, however a number of limitations must be addressed in future studies. Most current studies are relatively small and cross sectional; prospective, longitudinal studies across injury severity, and populations are needed to track exosome cargo changes after injury. Standardized exosome isolation as well as advancement in identifying/isolating exosomes from CNS-specific tissue sources will improve mechanistic understanding of cargo changes as well as reliability of findings. Exosomes are also just beginning to be used in model systems to understand functional effects of TBI-associated cargo such as toxicity. Finally linking exosome cargo changes to objective markers of neuronal pathology and cognitive changes will be critical in validating these tools to provide insights into injury and recovery states after TBI.

Keywords: biomarkers; cytokines; exosome; miRNA; mild traumatic brain injury.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Exosome Release Schematic. EVs are released by neurons and glia. Their cargo often contains protein, cytokines, and/or miRNA. These exosomes can cross the blood brain barrier and enter the peripheral bloodstream, allowing for quantification and study. This figure was created using the Mind the Graph online platform (www.mindthegraph.com).
See this image and copyright information in PMC

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