| Autor: |
Emma Partiot, Barbara Gorda, Willy Lutz, Solène Lebrun, Pierre Khalfi, Stéphan Mora, Benoit Charlot, Karim Majzoub, Solange Desagher, Gowrishankar Ganesh, Sophie Colomb, Raphael Gaudin |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
EMBO Molecular Medicine, Vol 16, Iss 4, Pp 1004-1026 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1757-4684 |
| DOI: |
10.1038/s44321-024-00039-9 |
| Popis: |
Abstract Viral neuroinfections represent a major health burden for which the development of antivirals is needed. Antiviral compounds that target the consequences of a brain infection (symptomatic treatment) rather than the cause (direct-acting antivirals) constitute a promising mitigation strategy that requires to be investigated in relevant models. However, physiological surrogates mimicking an adult human cortex are lacking, limiting our understanding of the mechanisms associated with viro-induced neurological disorders. Here, we optimized the Organotypic culture of Post-mortem Adult human cortical Brain explants (OPAB) as a preclinical platform for Artificial Intelligence (AI)-driven antiviral studies. OPAB shows robust viability over weeks, well-preserved 3D cytoarchitecture, viral permissiveness, and spontaneous local field potential (LFP). Using LFP as a surrogate for neurohealth, we developed a machine learning framework to predict with high confidence the infection status of OPAB. As a proof-of-concept, we showed that antiviral-treated OPAB could partially restore LFP-based electrical activity of infected OPAB in a donor-dependent manner. Together, we propose OPAB as a physiologically relevant and versatile model to study neuroinfections and beyond, providing a platform for preclinical drug discovery. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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