Biofluid-based predictors of post-concussion symptoms: A narrative review of mild traumatic brain injury biomarkers

Research output: Contribution to journalReview articlepeer-review

Abstract

Mild traumatic brain injury can disrupt brain function and is associated with high morbidity and healthcare utilization. While many individuals recover from mild traumatic brain injury, a significant proportion experience long-term sequelae, collectively known as post-concussion syndrome. Symptoms of post-concussion syndrome include headache, dizziness, insomnia, cognitive processing difficulties and mental health disturbances. The disease burden is augmented by the current lack of objective measures to accurately predict long-term symptoms and deficits, providing an opportunity to utilize biomarkers in biofluids. A large proportion of available diagnostic clinical tools are subjective symptom scores. This review aims to explore current fluid biomarkers, grouped by clinical symptoms. With the available literature, we have discovered a wide range of fluid biomarkers that have been investigated for predicting post-traumatic headache, including neuropeptides; sleep disturbances, such as cortisol and melatonin; vestibular disturbances, including interleukin-6 and neurone-specific enolase; and vomiting, such as S100B. Along with physical symptoms, biomarkers investigated for predicting cognitive disturbances include inflammatory markers, S100B, neurofilament light chain, tau, microRNA and hormones. Biomarkers to predict mental health disturbances may include brain-derived neurotrophic factor, tau and cortisol. By utilizing such biomarkers, there is capacity to adopt a personalized medicine approach to facilitate early interventions for those most in need while also identifying individuals with a favourable prognosis who can safely return to their normal activities.

Original languageEnglish
Article numberfcaf501
Number of pages17
JournalBrain Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 18 Dec 2025

Bibliographical note

© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse,
distribution, and reproduction in any medium, provided the original work is properly cited.

Data Access Statement

Data sharing is not applicable as no primary data were generated from this review.

Funding

This work is funded by the UK mTBI-Predict consortia grant from the Ministry of Defence (MoD; contract numbers Y1 701577555, Y2 705737453) and Department of Defense (DoD; grant number BA230047).

Keywords

  • biofluids
  • biomarkers
  • mTBI
  • post-concussion syndrome

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