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Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications

Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain injury (TBI). A better understanding of their role in the diagnosis, characterization, and management of TBI is essential for upcoming clinical implementation. In the current investigation, we aimed to explore...

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Autores principales: Mondello, Stefania, Guedes, Vivian A., Lai, Chen, Czeiter, Endre, Amrein, Krisztina, Kobeissy, Firas, Mechref, Yehia, Jeromin, Andreas, Mithani, Sara, Martin, Carina, Wagner, Chelsea L., Czigler, András, Tóth, Luca, Fazekas, Bálint, Buki, Andras, Gill, Jessica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227241/
https://www.ncbi.nlm.nih.gov/pubmed/32326450
http://dx.doi.org/10.3390/cells9040977
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author Mondello, Stefania
Guedes, Vivian A.
Lai, Chen
Czeiter, Endre
Amrein, Krisztina
Kobeissy, Firas
Mechref, Yehia
Jeromin, Andreas
Mithani, Sara
Martin, Carina
Wagner, Chelsea L.
Czigler, András
Tóth, Luca
Fazekas, Bálint
Buki, Andras
Gill, Jessica
author_facet Mondello, Stefania
Guedes, Vivian A.
Lai, Chen
Czeiter, Endre
Amrein, Krisztina
Kobeissy, Firas
Mechref, Yehia
Jeromin, Andreas
Mithani, Sara
Martin, Carina
Wagner, Chelsea L.
Czigler, András
Tóth, Luca
Fazekas, Bálint
Buki, Andras
Gill, Jessica
author_sort Mondello, Stefania
collection PubMed
description Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain injury (TBI). A better understanding of their role in the diagnosis, characterization, and management of TBI is essential for upcoming clinical implementation. In the current investigation, we aimed to explore longitudinal trajectories of brain injury exosomal proteins in blood of patients with moderate-to-severe TBI, and to evaluate the relation with the free-circulating counterpart and patient imaging and clinical parameters. Exosomal levels of glial (glial fibrillary acidic protein (GFAP)) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and total-tau (t-tau)) proteins were measured in serum of 21 patients for up 5 days after injury using single molecule array (Simoa) technology. Group-based trajectory analysis was used to generate distinct temporal exosomal biomarker profiles. We found altered profiles of serum brain injury exosomal proteins following injury. The dynamics and levels of exosomal and related free-circulating markers, although correlated, showed differences. Patients with diffuse injury displayed higher acute exosomal NFL and GFAP concentrations in serum than those with focal lesions. Exosomal UCH-L1 profile characterized by acutely elevated values and a secondary steep rise was associated with early mortality (n = 2) with a sensitivity and specificity of 100%. Serum brain injury exosomal proteins yielded important diagnostic and prognostic information and represent a novel means to unveil underlying pathophysiology in patients with moderate-to-severe TBI. Our findings support their utility as potential tools to improve patient phenotyping in clinical practice and therapeutic trials.
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spelling pubmed-72272412020-05-28 Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications Mondello, Stefania Guedes, Vivian A. Lai, Chen Czeiter, Endre Amrein, Krisztina Kobeissy, Firas Mechref, Yehia Jeromin, Andreas Mithani, Sara Martin, Carina Wagner, Chelsea L. Czigler, András Tóth, Luca Fazekas, Bálint Buki, Andras Gill, Jessica Cells Article Brain injury exosomal proteins are promising blood biomarker candidates in traumatic brain injury (TBI). A better understanding of their role in the diagnosis, characterization, and management of TBI is essential for upcoming clinical implementation. In the current investigation, we aimed to explore longitudinal trajectories of brain injury exosomal proteins in blood of patients with moderate-to-severe TBI, and to evaluate the relation with the free-circulating counterpart and patient imaging and clinical parameters. Exosomal levels of glial (glial fibrillary acidic protein (GFAP)) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and total-tau (t-tau)) proteins were measured in serum of 21 patients for up 5 days after injury using single molecule array (Simoa) technology. Group-based trajectory analysis was used to generate distinct temporal exosomal biomarker profiles. We found altered profiles of serum brain injury exosomal proteins following injury. The dynamics and levels of exosomal and related free-circulating markers, although correlated, showed differences. Patients with diffuse injury displayed higher acute exosomal NFL and GFAP concentrations in serum than those with focal lesions. Exosomal UCH-L1 profile characterized by acutely elevated values and a secondary steep rise was associated with early mortality (n = 2) with a sensitivity and specificity of 100%. Serum brain injury exosomal proteins yielded important diagnostic and prognostic information and represent a novel means to unveil underlying pathophysiology in patients with moderate-to-severe TBI. Our findings support their utility as potential tools to improve patient phenotyping in clinical practice and therapeutic trials. MDPI 2020-04-15 /pmc/articles/PMC7227241/ /pubmed/32326450 http://dx.doi.org/10.3390/cells9040977 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mondello, Stefania
Guedes, Vivian A.
Lai, Chen
Czeiter, Endre
Amrein, Krisztina
Kobeissy, Firas
Mechref, Yehia
Jeromin, Andreas
Mithani, Sara
Martin, Carina
Wagner, Chelsea L.
Czigler, András
Tóth, Luca
Fazekas, Bálint
Buki, Andras
Gill, Jessica
Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications
title Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications
title_full Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications
title_fullStr Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications
title_full_unstemmed Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications
title_short Circulating Brain Injury Exosomal Proteins following Moderate-to-Severe Traumatic Brain Injury: Temporal Profile, Outcome Prediction and Therapy Implications
title_sort circulating brain injury exosomal proteins following moderate-to-severe traumatic brain injury: temporal profile, outcome prediction and therapy implications
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227241/
https://www.ncbi.nlm.nih.gov/pubmed/32326450
http://dx.doi.org/10.3390/cells9040977
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