Research Progress of Blood Biomarkers for Prognosis of Traumatic Brain Injury

Abstract Objective: This study examines the relationship of serum total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1), and glial fibrillary acidic protein (GFAP) with neurocognitive performance in service members and veterans with a history of traumatic brain injury (TBI). Method: Service members (n = 488) with a history of uncomplicated mild (n = 172), complicated mild, moderate, severe, or penetrating TBI (sTBI; n = 126), injured controls (n = 116), and non-injured controls (n = 74) prospectively enrolled from Military Treatment Facilities. Participants completed a blood draw and neuropsychological assessment a year or more post-injury. Six neuropsychological composite scores and presence/absence of mild neurocognitive disorder (MNCD) were evaluated. Within each group, stepwise hierarchical regression models were conducted. Results: Within the sTBI group, increased serum UCH-L1 was related to worse immediate memory and delayed memory (R2Δ = .065–.084, ps < .05) performance, while increased GFAP was related to worse perceptual reasoning (R2Δ = .030, p = .036). Unexpectedly, within injured controls, UCH-L1 and GFAP were inversely related to working memory (R2Δ = .052–.071, ps < .05), and NFL was related to executive functioning (R2Δ = .039, p = .021) and MNCD (Exp(B) = 1.119, p = .029). Conclusions: Results suggest GFAP and UCH-L1 could play a role in predicting poor cognitive outcome following complicated mild and more severe TBI. Further investigation of blood biomarkers and cognition is warranted.

Download Full-text

Blood biomarkers for assessment of mild traumatic brain injury and chronic traumatic encephalopathy

Biomarkers ◽

10.1080/1354750x.2020.1735521 ◽

2020 ◽

Vol 25 (3) ◽

pp. 213-227 ◽

Cited By ~ 1

Author(s):

Matthew I. Hiskens ◽

Anthony G. Schneiders ◽

Mariana Angoa-Pérez ◽

Rebecca K. Vella ◽

Andrew S. Fenning

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mild Traumatic Brain Injury ◽

Chronic Traumatic Encephalopathy ◽

Blood Biomarkers

Download Full-text

Blood biomarkers on admission in acute traumatic brain injury: Relations to severity, CT findings and care path in the CENTER-TBI study

EBioMedicine ◽

10.1016/j.ebiom.2020.102785 ◽

2020 ◽

Vol 56 ◽

pp. 102785 ◽

Cited By ~ 5

Author(s):

Endre Czeiter ◽

Krisztina Amrein ◽

Benjamin Y. Gravesteijn ◽

Fiona Lecky ◽

David K. Menon ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Blood Biomarkers ◽

Ct Findings ◽

Acute Traumatic Brain Injury ◽

Care Path

Download Full-text

Bioinformatic analysis of brain-specific miRNAs for identification of candidate traumatic brain injury blood biomarkers

10.1101/794321 ◽

2019 ◽

Author(s):

Christine Smothers ◽

Chris Winkelman ◽

Grant C. O’Connell

Keyword(s):

Traumatic Brain Injury ◽

Spinal Cord ◽

Brain Injury ◽

Brain Tissue ◽

Tissue Sample ◽

Surrogate Marker ◽

Final Analysis ◽

Blood Biomarkers ◽

Post Injury ◽

Original Analysis

AbstractBackgroundDetection of brain-specific miRNAs in the peripheral blood could serve as a surrogate marker of traumatic brain injury (TBI). Here, we systematically identified brain-enriched miRNAs, and tested their utility for use as TBI biomarkers in the acute phase of care.MethodsPublically-available microarray data generated from 31 postmortem human tissues was used to rank 1,364 miRNAs in terms of their degree of brain-specific expression. Levels of the top five ranked miRNAs were then prospectively measured in serum samples collected from 10 TBI patients at hospital admission, as well as from 10 controls.ResultsThe top five miRNAs identified in our analysis (miR-137, miR-219a-5p, miR-128-3p, miR-124-3p, and miR-138-5p) exhibited 31 to 74-fold higher expression in brain relative to other tissues. Furthermore, their levels were elevated in serum from TBI patients compared to controls, and were collectively able to discriminate between groups with 90% sensitivity and 80% specificity. Subsequent informatic pathway analysis revealed that their target transcripts were significantly enriched for components of signaling pathways which are active in peripheral organs such as the heart.ConclusionsThe five candidate miRNAs identified in this study have promise as blood biomarkers of TBI, and could also be molecular contributors to systemic physiologic changes commonly observed post-injury.A FINAL PEER REVIEWED VERSION OF THIS ARTICLE HAS BEEN PUBLISHED IN BRAIN INJURY AT THE FOLLOWING DOI: 10.1080/02699052.2020.1764102There are some notable differences between the analysis presented in this preprint and our final peer-reviewed article. There was a single tissue sample originating from spinal cord that we had classified as a non-brain tissue in our original analysis outlined in this preprint. Because the composition of spinal cord and brain are highly similar in terms of gene expression, classifying this sample as a non-brain tissue dramatically reduced the levels of brain enrichment observed in the analysis. Because brain and spinal cord are molecularly highly similar, but technically distinct anatomical structures, we simply decided to exclude this sample from our final analysis published in Brain Injury to avoid confounds. The top 5 miRNAs identified in our original analysis still fell within the top 7 of this final analysis. In addition, the final analysis identified two additional miRNAs which could be candidate biomarkers based on levels of brain enrichment.The final article published in Brain Injury also reports an additional confirmatory tissue specificity analysis performed in a second independent dataset, as well as additional analysis examining the brain specificity of several notable previously proposed miRNA TBI biomarkers, which is not described in this preprint.

Download Full-text