scholarly journals Plasma extracellular vesicles as a source of biomarkers in traumatic brain injury

2020 ◽  
pp. 1-8
Author(s):  
Ross C. Puffer ◽  
Luz M. Cumba Garcia ◽  
Benjamin T. Himes ◽  
Mi-Yeon Jung ◽  
Frederic B. Meyer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Extracellular Vesicles ◽  
Noncoding Rna ◽  
Altered Consciousness ◽  
Biologically Relevant ◽  
Potential Biomarker ◽  
Diagnosis And Classification ◽  
Novel Biomarkers ◽  
Organismal Development

OBJECTIVEThe objective of this study was to isolate extracellular vesicles (EVs) from plasma in a cohort of patients with traumatic brain injury (TBI) and analyze their contents for novel biomarkers that could prove useful for rapid diagnosis and classification of brain injury during initial evaluation.METHODSPlasma EVs were isolated by serial ultracentrifugation from patients with TBI (n = 15) and healthy controls (n = 5). Samples were obtained from the TRACK-TBI biorepository (2010–present). Size and concentration were determined by nanoparticle tracking. Glial fibrillary acidic protein (GFAP) concentration was determined in EV protein. EV RNA was isolated and deep sequencing of short noncoding RNA was performed.RESULTSPlasma EVs are physically similar but contained approximately 10 times more GFAP in TBI patients with altered consciousness than patients and controls with normal consciousness. Eleven highly differentially expressed microRNAs (miRNAs) were identified between these groups. Genes targeted by these miRNAs are highly associated with biologically relevant cellular pathways, including organismal injury, cellular development, and organismal development. Multiple additional coding and noncoding RNA species with potential biomarker utility were identified.CONCLUSIONSIsolating plasma EVs in patients with TBI is feasible. Increased GFAP concentration—a validated plasma TBI marker—in EVs from TBI patients with altered consciousness, along with differential expression of multiple miRNAs targeting TBI-relevant pathways, suggests that EVs may be a useful source of TBI biomarkers. Additional evaluation in larger patient cohorts is indicated.

scholarly journals Micro Ribonucleic Acid Profiles of Traumatic Brain Injury Isolated From Plasma Extracellular Vesicles

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Ross Puffer ◽  
Luz Cumba-Garcia ◽  
Benjamin T Himes ◽  
David O Okonkwo ◽  
Ian F Parney
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Extracellular Vesicles ◽  
Rna Isolation ◽  
Extracellular Vesicle ◽  
Micro Rna ◽  
Altered Consciousness ◽  
Rna Sequences ◽  
Altered Level ◽  
Level Of Consciousness

Abstract INTRODUCTION Extracellular vesicles (EVs) are membrane-bound particles released by the majority of human cells, including cells within the central nervous system. They may represent a diagnostic or prognostic target obtainable in peripheral blood of neurotrauma patients. We have isolated micro RNA sequences contained within EVs of 15 patients with traumatic brain injury (TBI) and compared them to miRNA sequences from 5 healthy controls. METHODS Extracellular vesicles were isolated from 15 TBI subjects, including 6 mild TBI (Glasgow Coma Scale (GCS) 13-15), 3 moderate TBI (GCS 9-12), and 6 severe TBI (GCS 3-8), as well as 5 healthy control. EVs were analyzed using nanoparticle tracking analysis. Samples underwent RNA isolation and extraction, followed by miRNA sequencing and analysis. RESULTS TBI patients presenting with an altered level of consciousness (GCS = 14) had a significantly higher mean extracellular vesicle size compared to subjects with normal GCS (mean + /− sem = 108.3 nm + /− 7.7 nm vs 89.2 nm + /− 6.7 nm; P < .04). GFAP ELISA of the samples demonstrated significantly higher GFAP concentration in subjects with altered level of consciousness (GCS = 14) as compared to those with normal GCS (mean + /− sem GFAP concentration 2204.2 pg/mL + /− 1067.2 pg/mL vs. 207.8 pg/mL + /− 270.8 pg/mL, P = .05). We identified 9 miRNA sequences that were found in a significantly higher proportion in patients with altered consciousness compared to controls, as well as 2 miRNA sequences that were significantly downregulated in subjects with altered consciousness as compared to controls. CONCLUSION EVs may contain brain specific biomarkers that are released in greater quantities after TBI. These molecules can be isolated from plasma and sequenced. Further analysis will better elucidate the final pathways affected by these up and downregulated miRNA sequences. Analysis of EVs in subjects with TBI may allow for the identification of novel diagnostic and potentially prognostic biomarkers.

scholarly journals The role of salivary vesicles as a potential inflammatory biomarker to detect traumatic brain injury in mixed martial artists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rani Matuk ◽  
Mandy Pereira ◽  
Janette Baird ◽  
Mark Dooner ◽  
Yan Cheng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Head Injury ◽  
Injury Severity ◽  
Expression Profiles ◽  
High Impact ◽  
Impact Mechanism ◽  
Inflammatory Biomarker ◽  
Potential Biomarker

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.

scholarly journals Long noncoding RNA MALAT1 in exosomes drives regenerative function and modulates inflammation-linked networks following traumatic brain injury

2018 ◽  
Vol 15 (1) ◽  
Author(s):  
Niketa A. Patel ◽  
Lauren Daly Moss ◽  
Jea-Young Lee ◽  
Naoki Tajiri ◽  
Sandra Acosta ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Long Noncoding Rna ◽  
Noncoding Rna

scholarly journals Potential biomarkers to detect traumatic brain injury by the profiling of salivary extracellular vesicles

2019 ◽  
Vol 234 (8) ◽  
pp. 14377-14388 ◽  
Author(s):  
Yan Cheng ◽  
Mandy Pereira ◽  
Neha Raukar ◽  
John L. Reagan ◽  
Mathew Queseneberry ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Extracellular Vesicles ◽  
Potential Biomarkers

scholarly journals Diverging white matter trajectories in children after traumatic brain injury

Neurology ◽  
2017 ◽  
Vol 88 (15) ◽  
pp. 1392-1399 ◽  
Author(s):  
Emily L. Dennis ◽  
Faisal Rashid ◽  
Monica U. Ellis ◽  
Talin Babikian ◽  
Roza M. Vlasova ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
White Matter ◽  
Chronic Phase ◽  
Event Related Potentials ◽  
Preliminary Evidence ◽  
Healthy Controls ◽  
Potential Biomarker ◽  
Related Potentials ◽  
Healthy Control

Objective:To examine longitudinal trajectories of white matter organization in pediatric moderate/severe traumatic brain injury (msTBI) over a 12-month period.Methods:We studied 21 children (16 M/5 F) with msTBI, assessed 2–5 months postinjury and again 13–19 months postinjury, as well as 20 well-matched healthy control children. We assessed corpus callosum function through interhemispheric transfer time (IHTT), measured using event-related potentials, and related this to diffusion-weighted MRI measures of white matter (WM) microstructure. At the first time point, half of the patients with TBI had significantly slower IHTT (TBI-slow-IHTT, n = 11) and half were in the normal range (TBI-normal-IHTT, n = 10).Results:The TBI-normal-IHTT group did not differ significantly from healthy controls, either in WM organization in the chronic phase or in the longitudinal trajectory of WM organization between the 2 evaluations. In contrast, the WM organization of the TBI-slow-IHTT group was significantly lower than in healthy controls across a large portion of the WM. Longitudinal analyses showed that the TBI-slow-IHTT group experienced a progressive decline between the 2 evaluations in WM organization throughout the brain.Conclusions:We present preliminary evidence suggesting a potential biomarker that identifies a subset of patients with impaired callosal organization in the first months postinjury who subsequently experience widespread continuing and progressive degeneration in the first year postinjury.

scholarly journals Extracellular Vesicles Mediate Neuroprotection and Functional Recovery after Traumatic Brain Injury

2020 ◽  
Vol 37 (11) ◽  
pp. 1358-1369 ◽  
Author(s):  
Min Kyoung Sun ◽  
Austin P. Passaro ◽  
Charles-Francois Latchoumane ◽  
Samantha E. Spellicy ◽  
Michael Bowler ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Extracellular Vesicles ◽  
Functional Recovery

Overexpression of long noncoding RNA Malat1 ameliorates traumatic brain injury induced brain edema by inhibiting AQP4 and the NF‐κB/IL‐6 pathway

2019 ◽  
Vol 120 (10) ◽  
pp. 17584-17592 ◽  
Author(s):  
Yamin Zhang ◽  
Jianping Wang ◽  
Yi Zhang ◽  
Jia Wei ◽  
Ruipeng Wu ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Long Noncoding Rna ◽  
Noncoding Rna

scholarly journals Serum Amyloid A Protein as a Potential Biomarker for Severity and Acute Outcome in Traumatic Brain Injury

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Evan Wicker ◽  
Leah Benton ◽  
Kershina George ◽  
William Furlow ◽  
Sonia Villapol
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Serum Amyloid A ◽  
Protein Detection ◽  
Serum Amyloid ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lesion Volume ◽  
Amyloid A ◽  
Potential Biomarker ◽  
Serum Amyloid A Protein

Traumatic brain injury (TBI) causes a wide variety of neuroinflammatory events. These neuroinflammatory events depend, to a greater extent, on the severity of the damage. Our previous studies have shown that the liver produces serum amyloid A (SAA) at high levels in the initial hours after controlled cortical impact (CCI) injury in mice. Clinical studies have reported detectable SAA in the plasma of brain injury patients, but it is not clear if SAA levels depend on TBI severity. To evaluate this question, we performed a mild to severe CCI injury in wild-type mice. We collected blood samples and brains at 1, 3, and 7 days after injury for protein detection by western blotting, enzyme-linked immunosorbent assay, or immunohistochemical analysis. Our results showed that severe CCI injury compared to mild CCI injury or sham mice caused an increased neuronal death, larger lesion volume, increased microglia/macrophage density, and augmented neutrophil infiltration. Furthermore, we found that the serum levels of SAA protein ascended in the blood in correlation with high neuroinflammatory and neurodegenerative responses. Altogether, these results suggest that serum SAA may be a novel neuroinflammation-based, and severity-dependent, biomarker for acute TBI.

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