Gliotoxin penetrates and impairs the integrity of the human blood-brain barrier in vitro

Mycotoxin Research
Ronak PatelAbraham Jacob Al-Ahmad

Abstract

Cerebral fungal infections represent an important public health concern, where a key element of pathophysiology is the ability of the fungi to cross the blood-brain barrier (BBB). Yet the mechanism used by micro-organisms to cross such a barrier and invade the brain parenchyma remains unclear. This study investigated the effects of gliotoxin (GTX), a mycotoxin secreted by Aspergillus fumigatus, on the BBB using brain microvascular endothelial cells (BMECs) derived from induced pluripotent stem cells (iPSCs). We observed that both acute (2 h) and prolonged (24 h) exposure to GTX at the level of 1 μM or higher compromised BMECs monolayer integrity. Notably, acute exposure was sufficient to disrupt the barrier function in iPSC-derived BMECs, resulting in decreased transendothelial electrical resistance (TEER) and increased fluorescein permeability. Further, our data suggest that such disruption occurred without affecting tight junction complexes, via alteration of cell-matrix interactions, alterations in F-actin distribution, through a protein kinase C-independent signaling. In addition to its effect on the barrier function, we have observed a low permeability of GTX across the BBB. This fact can be partially explained by possible...Continue Reading

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Citations

Jul 31, 2019·Toxins·Thais Fernanda de Campos Fraga-SilvaAlexandrina Sartori
Jan 31, 2020·Frontiers in Microbiology·Zsolt RádulyLászló Csernoch
Apr 24, 2020·Fluids and Barriers of the CNS·Michael J Workman, Clive N Svendsen
Feb 15, 2020·New Zealand Veterinary Journal·T W Jordan
Jan 16, 2021·Cellular and Molecular Life Sciences : CMLS·Ashley B Strickland, Meiqing Shi
Feb 2, 2021·FEMS Microbiology Reviews·Antonia LastBernhard Hube
Oct 4, 2020·Neurochemistry International·Maryam VasefiAnthony Osu
Jul 28, 2020·Molecular and Cellular Neurosciences·Louise DelsingHenrik Zetterberg
Dec 30, 2018·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Shyanne PageAbraham Al-Ahmad

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Methods Mentioned

BETA
ELISA
PMA

Key Resources (RRID) Mentioned

AB_2533101
AB_1070651
AB_262133

Software Mentioned

TEER
ImageJ
Prism
Leica Acquisition Suite X

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