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

• Published in: Frontiers in neuroscience Vol. 17; p. 1189615
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 15-06-2023; Frontiers Media S.A
• Subjects: 3D neural tissue; Animal models; Biochip products; Biomarkers; Cell death; Electrodes; Electrophysiology; multiplex protein assays; Neuroimaging; Neuronal-glial interactions; Neuroscience; optical projection tomography; Parenchyma; Software; Stem cells; Trauma; Traumatic brain injury; in vitro model; electrophysiology; 3D neural tissue; biomarkers; traumatic brain injury; multiplex protein assays; optical projection tomography
• ISSN: 1662-4548; 1662-453X; 1662-453X
• DOI: 10.3389/fnins.2023.1189615

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
and animal-based
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
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.