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 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 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 Electrophysiological correlates of thalamocortical function in acute severe traumatic brain injury

2021 ◽  
Author(s):  
William H. Curley ◽  
Yelena G. Bodien ◽  
David W. Zhou ◽  
Mary M. Conte ◽  
Andrea S. Foulkes ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Severe Traumatic Brain Injury ◽  
Resting State ◽  
Chronic Phase ◽  
Post Injury ◽  
Network Function ◽  
Power Spectral ◽  
Level Of Consciousness ◽  
Thalamocortical Network

Few reliable biomarkers of consciousness exist for patients with acute severe brain injury. Tools assaying the neural networks that modulate consciousness may allow for tracking of recovery. The mesocircuit model, and its instantiation as the ABCD framework, classifies resting-state EEG power spectral densities into categories reflecting widely separated levels of thalamocortical network function and correlates with outcome in post-cardiac arrest coma. We applied the ABCD framework to acute severe traumatic brain injury and tested four hypotheses: 1) EEG channel-level ABCD classifications are spatially heterogeneous and temporally variable; 2) ABCD classifications improve longitudinally, commensurate with the degree of behavioural recovery; 3) ABCD classifications correlate with behavioural level of consciousness; and 4) the Coma Recovery Scale-Revised arousal facilitation protocol improves EEG dynamics along the ABCD scale. In this longitudinal cohort study, we enrolled 20 patients with acute severe traumatic brain injury requiring intensive care and 16 healthy controls. Through visual inspection, channel-level spectra from resting-state EEG were classified based on spectral peaks within frequency bands defined by the ABCD framework: A = no peaks above delta (<4 Hz) range (complete thalamocortical disruption); B = theta (4-8 Hz) peak (severe thalamocortical disruption); C = theta and beta (13-24 Hz) peaks (moderate thalamocortical disruption); or D = alpha (8-13 Hz) and beta peaks (normal thalamocortical function). We assessed behavioural level of consciousness with the Coma Recovery Scale-Revised or neurological examination and, in 12 patients, performed repeat EEG and behavioural assessments at ≥6-months post-injury. Acutely, 95% of patients demonstrated D signals in at least one channel but exhibited heterogeneity in the proportion of different channel-level ABCD classifications (mean percent D signals: 37%, range: 0-90%). By contrast, healthy participants and patients at follow-up predominantly demonstrated signals corresponding to intact thalamocortical network function (mean percent D signals: 94%). In patients studied acutely, ABCD classifications improved after the Coma Recovery Scale-Revised arousal facilitation protocol (P<0.05), providing electrophysiological evidence for the effectiveness of this commonly performed technique. ABCD classification did not correspond with behavioural level of consciousness acutely, where patients demonstrated substantial within-session temporal variability in ABCD classifications. However, ABCD classification distinguished patients with and without command-following in the subacute-to-chronic phase of recovery (P<0.01). Patients also demonstrated significant longitudinal improvement in EEG dynamics along the ABCD scale (median change in D signals: 37%, P<0.05). These findings support the use of the ABCD framework to characterize channel-level EEG dynamics and track fluctuations in functional thalamocortical network integrity in spatial detail.

scholarly journals Effect of Right Median Nerve Stimulation on Level of Consciousness in Traumatic Brain Injury Subjects

2016 ◽  
Vol 8 (3) ◽  
pp. 67
Author(s):  
Sirisha Nekkanti ◽  
Rahul Shaik ◽  
Srinivas Mondem ◽  
Nandini Meruva ◽  
Gunathevan Elumalai
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Median Nerve ◽  
Nerve Stimulation ◽  
Control Group ◽  
Coma Scale ◽  
Median Nerve Stimulation ◽  
Significant Difference ◽  
Level Of Consciousness ◽  
Experimental Group

<p class="Default"><strong>Background</strong>: The median nerve serves a peripheral gateway to the central nervous system. Median nerve stimulation is positively associated with regaining the level of consciousness in patients with traumatic brain injury, but the level of evidence is still a research question. So the purpose of the study is to find out the effectiveness of right median nerve stimulation on the level of consciousness and the relation between them in subjects with traumatic brain injury.<strong> Methodology: </strong>Twenty subjects with traumatic brain injury of axonal type were selected for study and randomized into two groups. Experimental group received right median nerve stimulation along with medications where as control group received medications only one month, 30 minutes a day. Glasgow coma scale is used to assess the changes in conscious levels<strong>. Result: </strong>The results have revealed that there is significance improvement noted in experimental group when compared to control group. Comparison  of Glassgow coma scale scores between experimental and control groups after one month showed significant difference with a P value 0.0261.<strong> Conclusion: </strong>Right median nerve stimulation is strongly associated with improvement of consciousness in patients with traumatic brain injury.</p><p><strong> </strong></p><p><strong> </strong></p>

scholarly journals Time-dependent cytokine and chemokine changes in mouse cerebral cortex following a mild traumatic brain injury

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
David Tweedie ◽  
Hanuma Kumar Karnati ◽  
Roger Mullins ◽  
Chaim G Pick ◽  
Barry J Hoffer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Extracellular Vesicle ◽  
Neurological Dysfunction ◽  
Physiological Processes ◽  
Mouse Cerebral Cortex ◽  
Weight Drop ◽  
Altered Proteins ◽  
Response Biomarkers ◽  
Global Health Problem

Traumatic brain injury (TBI) is a serious global health problem, many individuals live with TBI-related neurological dysfunction. A lack of biomarkers of TBI has impeded medication development. To identify new potential biomarkers, we time-dependently evaluated mouse brain tissue and neuronally derived plasma extracellular vesicle proteins in a mild model of TBI with parallels to concussive head injury. Mice (CD-1, 30–40 g) received a sham procedure or 30 g weight-drop and were euthanized 8, 24, 48, 72, 96 hr, 7, 14 and 30 days later. We quantified ipsilateral cortical proteins, many of which differed from sham by 8 hours post-mTBI, particularly GAS-1 and VEGF-B were increased while CXCL16 reduced, 23 proteins changed in 4 or more of the time points. Gene ontology pathways mapped from altered proteins over time related to pathological and physiological processes. Validation of proteins identified in this study may provide utility as treatment response biomarkers.

scholarly journals Differential MicroRNA Expression of miR-21 and miR-155 within Oral Cancer Extracellular Vesicles in Response to Melatonin

2019 ◽  
Vol 7 (2) ◽  
pp. 48 ◽  
Author(s):  
Matthew Hunsaker ◽  
Greta Barba ◽  
Karl Kingsley ◽  
Katherine M. Howard
Keyword(s):  
Oral Cancer ◽  
Cell Lines ◽  
Extracellular Vesicles ◽  
Rna Isolation ◽  
Extracellular Vesicle ◽  
Primary Objective ◽  
Microrna Expression ◽  
Bioactive Molecules ◽  
Melatonin Administration ◽  
Mirna Content

Objective: Extracellular vesicles derived from oral cancer cells, which include Exosomes and Oncosomes, are membranous vesicles secreted into the surrounding extracellular environment. These extracellular vesicles can regulate and modulate oral squamous cell carcinoma (OSCC) progression through the horizontal transfer of bioactive molecules including proteins, lipids and microRNA (miRNA). The primary objective of this study was to examine the potential to isolate and evaluate extracellular vesicles (including exosomes) from various oral cancer cell lines and to explore potential differences in miRNA content. Methods: The OSCC cell lines SCC9, SCC25 and CAL27 were cultured in DMEM containing 10% exosome-free fetal bovine serum. Cell-culture conditioned media was collected for exosome and extracellular vesicle isolation after 72 h. Isolation was completed using the Total Exosome Isolation reagent (Invitrogen) and extracellular vesicle RNA was purified using the Total Exosome RNA isolation kit (Invitrogen). Extracellular vesicle miRNA content was evaluated using primers specific for miR-16, -21, -133a and -155. Results: Extracellular vesicles were successfully isolated from all three OSCC cell lines and total extracellular vesicle RNA was isolated. Molecular screening using primers specific for several miRNA revealed differential baseline expression among the different cell lines. The addition of melatonin significantly reduced the expression of miR-155 in all of the OSCC extracellular vesicles. However, miR-21 was significantly increased in each of the three OSCC isolates. No significant changes in miR-133a expression were observed under melatonin administration. Conclusions: Although many studies have documented changes in gene expression among various cancers under melatonin administration, few studies have evaluated these effects on microRNAs. These results may be among the first to evaluate the effects of melatonin on microRNA expression in oral cancers, which suggests the differential modulation of specific microRNAs, such as miR-21, miR-133a and miR-155, may be of significant importance when evaluating the mechanisms and pathways involved in melatonin-associated anti-tumor effects.

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
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