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© Institut Pasteur
Culture de myotubes murins infectés par le virus de la rage fixe, observée en immunoflorescence indirecte.
Publication : Journal of visualized experiments : JoVE

A Human Blood-Brain Interface Model to Study Barrier Crossings by Pathogens or Medicines and Their Interactions with the Brain

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Journal of visualized experiments : JoVE - 09 Apr 2019

da Costa A, Prehaud C, Bakoa F, Afonso P, Ceccaldi PE, Lafaye P, Lafon M

Link to Pubmed [PMID] – 31033945

J Vis Exp 2019 Apr;(146)

The early screening of nervous system medicines on a pertinent and reliable in cellulo BBB model for their penetration and their interaction with the barrier and the brain parenchyma is still an unmet need. To fill this gap, we designed a 2D in cellulo model, the BBB-Minibrain, by combining a polyester porous membrane culture insert human BBB model with a Minibrain formed by a tri-culture of human brain cells (neurons, astrocytes and microglial cells). The BBB-Minibrain allowed us to test the transport of a neuroprotective drug candidate (e.g., Neurovita), through the BBB, to determine the specific targeting of this molecule to neurons and to show that the neuroprotective property of the drug was preserved after the drug had crossed the BBB. We have also demonstrated that BBB-Minibrain constitutes an interesting model to detect the passage of virus particles across the endothelial cells barrier and to monitor the infection of the Minibrain by neuroinvasive virus particles. The BBB-Minibrain is a reliable system, easy to handle for researcher trained in cell culture technology and predictive of the brain cells phenotypes after treatment or insult. The interest of such in cellulo testing would be twofold: introducing derisking steps early in the drug development on the one hand and reducing the use of animal testing on the other hand.

https://www.ncbi.nlm.nih.gov/pubmed/31033945