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

Frontiers in Neuroscience

Neuroscience

Marc E. Pfeifer¹  Ophélie Righini¹  Denis Prim¹  Milica Jovic´¹  Yoan Neuenschwander²  Jérôme Extermann²  Cédric Schmidt²  Adrien Roux³  Céline Loussert-Fonta³  Luc Stoppini³  Marc O. Heuschkel³  Loris Gomez Baisac³ 

[1] Diagnostic Systems Research Group, Institute of Life Technologies, School of Engineering, University of Applied Sciences and Arts Western Switzerland (HES-SO Valais-Wallis), Sion, Switzerland;Micro-Nanotechnology Group, HEPIA HES-SO University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland;Tissue Engineering Laboratory, HEPIA HES-SO University of Applied Sciences and Arts Western Switzerland, Geneva, Switzerland;

关键词: traumatic brain injury;    optical projection tomography;    3D neural tissue;    multiplex protein assays;    biomarkers;    electrophysiology;    in vitro;   

DOI  :  10.3389/fnins.2023.1189615

 received in 2023-03-19, accepted in 2023-05-09,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Loussert-Fonta, Stoppini, Neuenschwander, Righini, Prim, Schmidt, Heuschkel, Gomez Baisac, Jovic´, Pfeifer, Extermann and Roux.