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Proteomic discovery of prognostic protein biomarkers for persisting problems after mild traumatic brain injury.

ABSTRACT: Some individuals with mild traumatic brain injury (mTBI), also known as concussion, have neuropsychiatric and physical problems that last longer than a few months. Symptoms following mTBI are not only impacted by the kind and severity of the injury but also by the post-injury experience and the individual's responses to it, making the persistence of mTBI particularly difficult to predict. We aimed to identify prognostic blood-based protein biomarkers predicting 6-month outcomes, in light of the clinical course after the injury, in a longitudinal mTBI cohort (N = 42). Among 420 target proteins quantified by multiple-reaction monitoring-mass spectrometry assays of blood samples, 31, 43, and 15 proteins were significantly associated with the poor recovery of neuropsychological symptoms at < 72 h, 1 week, and 1 month after the injury, respectively. Sequential associations among clinical assessments (depressive symptoms and cognitive function) affecting the 6-month outcomes were evaluated. Then, candidate biomarker proteins indirectly affecting the outcome via neuropsychological symptoms were identified. Using the identified proteins, prognostic models that can predict the 6-month outcome of mTBI were developed. These protein biomarkers established in the context of the clinical course of mTBI may have potential for clinical application.

SUBMITTER: Lee MY

PROVIDER: S-EPMC10643618 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Proteomic discovery of prognostic protein biomarkers for persisting problems after mild traumatic brain injury.

Lee Min-Yong MY Son Minsoo M Lee Hyun Haeng HH Kang Min-Gu MG Yun Seo Jung SJ Seo Han Gil HG Kim Youngsoo Y Oh Byung-Mo BM

Scientific reports 20231113 1

Some individuals with mild traumatic brain injury (mTBI), also known as concussion, have neuropsychiatric and physical problems that last longer than a few months. Symptoms following mTBI are not only impacted by the kind and severity of the injury but also by the post-injury experience and the individual's responses to it, making the persistence of mTBI particularly difficult to predict. We aimed to identify prognostic blood-based protein biomarkers predicting 6-month outcomes, in light of the ...[more]

PMID: 37957236

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Project description:ObjectiveTo systematically review studies relating neuroimaging findings to balance problems resulting from a history of mTBI.IntroductionMild traumatic brain injury affects 55.9 million people worldwide every year. These injuries can have persistent symptoms such as maintaining balance which can be life-altering. Difficulties maintaining balance persist months or years after a mild traumatic brain injury in >30% of patients. Neuroimaging modalities, including magnetic resonance imaging, diffusion-weighted imaging, functional magnetic resonance imaging, electroencephalography, and magnetoencephalography, have been associated with presentation or persistence of balance difficulties, but no clinical guidelines are currently in place.Inclusion criteriaStudies will include participants of any age or sex who were diagnosed as having mild traumatic brain injury by a medical professional, excluding studies which by design included patients with other conditions diagnosed using neuroimaging findings. There must be at least one post-injury scan from at one or more of the included neuroimaging modalities, and assessment of balance problems. A comparator must be present in the form of either a control group or longitudinal design.MethodsA search will be conducted in Elsevier (Embase), MEDLINE (PubMed), Google Scholar, SportDiscus (EBSCOhost) and ProQuest for studies meeting the inclusion criteria, published 2013-2024, and available in English. Reviews will not be included. The process of study selection, critical assessment, data extraction, and summarizing findings will be conducted by two independent reviewers, with disagreements resolved by a third. The meta-analysis will summarize the strength of association between specific findings related to brain regions using various neuroimaging modalities and the presentation or persistence of balance difficulties. Evidence related to each neuroimaging modality will summarized using the GRADE approach.Trial registrationSystematic review registration number: CRD42024476988.

Project description:To investigate longitudinal changes in global and regional brain volume in patients 1 year after mild traumatic brain injury (MTBI) and to correlate such changes with clinical and neurocognitive metrics.This institutional review board-approved study was HIPAA compliant. Twenty-eight patients with MTBI (with 19 followed up at 1 year) with posttraumatic symptoms after injury and 22 matched control subjects (with 12 followed up at 1 year) were enrolled. Automated segmentation of brain regions to compute regional gray matter (GM) and white matter (WM) volumes was performed by using three-dimensional T1-weighted 3.0-T magnetic resonance imaging, and results were correlated with clinical metrics. Pearson and Spearman rank correlation coefficients were computed between longitudinal brain volume and neurocognitive scores, as well as clinical metrics, over the course of the follow-up period.One year after MTBI, there was measurable global brain atrophy, larger than that in control subjects. The anterior cingulate WM bilaterally and the left cingulate gyrus isthmus WM, as well as the right precuneal GM, showed significant decreases in regional volume in patients with MTBI over the 1st year after injury (corrected P < .05); this was confirmed by means of cross-sectional comparison with data in control subjects (corrected P < .05). Left and right rostral anterior cingulum WM volume loss correlated with changes in neurocognitive measures of memory (r = 0.65, P = .005) and attention (r = 0.60, P = .01). At 1-year follow-up, WM volume in the left cingulate gyrus isthmus correlated with clinical scores of anxiety (Spearman rank correlation r = -0.68, P = .007) and postconcussive symptoms (Spearman rank correlation r = -0.65, P = .01).These observations demonstrate structural changes to the brain 1 year after injury after a single concussive episode. Regional brain atrophy is not exclusive to moderate and severe traumatic brain injury but may be seen after mild injury. In particular, the anterior part of the cingulum and the cingulate gyrus isthmus, as well as the precuneal GM, may be distinctively vulnerable 1 year after MTBI.

Project description: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.

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Proteomic discovery of prognostic protein biomarkers for persisting problems after mild traumatic brain injury.

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Proteomic discovery of prognostic protein biomarkers for persisting problems after mild traumatic brain injury.

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