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Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device

Traumatic brain injury (TBI) is caused by a wide range of physical events and can induce an even larger spectrum of short- to long-term pathophysiologies. Neuroscientists have relied on animal models to understand the relationship between mechanical damages and functional alterations of neural cells...

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Autores principales: Loussert-Fonta, Céline, Stoppini, Luc, Neuenschwander, Yoan, Righini, Ophélie, Prim, Denis, Schmidt, Cédric, Heuschkel, Marc O., Gomez Baisac, Loris, Jovic´, Milica, Pfeifer, Marc E., Extermann, Jérôme, Roux, Adrien
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10308006/
https://www.ncbi.nlm.nih.gov/pubmed/37397462
http://dx.doi.org/10.3389/fnins.2023.1189615
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author Loussert-Fonta, Céline
Stoppini, Luc
Neuenschwander, Yoan
Righini, Ophélie
Prim, Denis
Schmidt, Cédric
Heuschkel, Marc O.
Gomez Baisac, Loris
Jovic´, Milica
Pfeifer, Marc E.
Extermann, Jérôme
Roux, Adrien
author_facet Loussert-Fonta, Céline
Stoppini, Luc
Neuenschwander, Yoan
Righini, Ophélie
Prim, Denis
Schmidt, Cédric
Heuschkel, Marc O.
Gomez Baisac, Loris
Jovic´, Milica
Pfeifer, Marc E.
Extermann, Jérôme
Roux, Adrien
author_sort Loussert-Fonta, Céline
collection PubMed
description Traumatic brain injury (TBI) is caused by a wide range of physical events and can induce an even larger spectrum of short- to long-term pathophysiologies. Neuroscientists have relied on animal models to understand the relationship between mechanical damages and functional alterations of neural cells. These in vivo and animal-based in vitro models represent important approaches to mimic traumas on whole brains or organized brain structures but are not fully representative of pathologies occurring after traumas on human brain parenchyma. To overcome these limitations and to establish a more accurate and comprehensive model of human TBI, we engineered an in vitro platform to induce injuries via the controlled projection of a small drop of liquid onto a 3D neural tissue engineered from human iPS cells. With this platform, biological mechanisms involved in neural cellular injury are recorded through electrophysiology measurements, quantification of biomarkers released, and two imaging methods [confocal laser scanning microscope (CLSM) and optical projection tomography (OPT)]. The results showed drastic changes in tissue electrophysiological activities and significant releases of glial and neuronal biomarkers. Tissue imaging allowed us to reconstruct the injured area spatially in 3D after staining it with specific nuclear dyes and to determine TBI resulting in cell death. In future experiments, we seek to monitor the effects of TBI-induced injuries over a prolonged time and at a higher temporal resolution to better understand the subtleties of the biomarker release kinetics and the cell recovery phases.
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spelling pubmed-103080062023-06-30 Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device Loussert-Fonta, Céline Stoppini, Luc Neuenschwander, Yoan Righini, Ophélie Prim, Denis Schmidt, Cédric Heuschkel, Marc O. Gomez Baisac, Loris Jovic´, Milica Pfeifer, Marc E. Extermann, Jérôme Roux, Adrien Front Neurosci Neuroscience Traumatic brain injury (TBI) is caused by a wide range of physical events and can induce an even larger spectrum of short- to long-term pathophysiologies. Neuroscientists have relied on animal models to understand the relationship between mechanical damages and functional alterations of neural cells. These in vivo and animal-based in vitro models represent important approaches to mimic traumas on whole brains or organized brain structures but are not fully representative of pathologies occurring after traumas on human brain parenchyma. To overcome these limitations and to establish a more accurate and comprehensive model of human TBI, we engineered an in vitro platform to induce injuries via the controlled projection of a small drop of liquid onto a 3D neural tissue engineered from human iPS cells. With this platform, biological mechanisms involved in neural cellular injury are recorded through electrophysiology measurements, quantification of biomarkers released, and two imaging methods [confocal laser scanning microscope (CLSM) and optical projection tomography (OPT)]. The results showed drastic changes in tissue electrophysiological activities and significant releases of glial and neuronal biomarkers. Tissue imaging allowed us to reconstruct the injured area spatially in 3D after staining it with specific nuclear dyes and to determine TBI resulting in cell death. In future experiments, we seek to monitor the effects of TBI-induced injuries over a prolonged time and at a higher temporal resolution to better understand the subtleties of the biomarker release kinetics and the cell recovery phases. Frontiers Media S.A. 2023-06-15 /pmc/articles/PMC10308006/ /pubmed/37397462 http://dx.doi.org/10.3389/fnins.2023.1189615 Text en Copyright © 2023 Loussert-Fonta, Stoppini, Neuenschwander, Righini, Prim, Schmidt, Heuschkel, Gomez Baisac, Jovic´, Pfeifer, Extermann and Roux. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Loussert-Fonta, Céline
Stoppini, Luc
Neuenschwander, Yoan
Righini, Ophélie
Prim, Denis
Schmidt, Cédric
Heuschkel, Marc O.
Gomez Baisac, Loris
Jovic´, Milica
Pfeifer, Marc E.
Extermann, Jérôme
Roux, Adrien
Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device
title Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device
title_full Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device
title_fullStr Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device
title_full_unstemmed Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device
title_short Opening the black box of traumatic brain injury: a holistic approach combining human 3D neural tissue and an in vitro traumatic brain injury induction device
title_sort opening the black box of traumatic brain injury: a holistic approach combining human 3d neural tissue and an in vitro traumatic brain injury induction device
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10308006/
https://www.ncbi.nlm.nih.gov/pubmed/37397462
http://dx.doi.org/10.3389/fnins.2023.1189615
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