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An In Vitro Model of the Blood–Brain Barrier: Naegleria fowleri Affects the Tight Junction Proteins and Activates the Microvascular Endothelial Cells
Author(s) -
CoronadoVelázquez Daniel,
Betanzos Abigail,
SerranoLuna Jesús,
Shibayama Mineko
Publication year - 2018
Publication title -
journal of eukaryotic microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.067
H-Index - 77
eISSN - 1550-7408
pISSN - 1066-5234
DOI - 10.1111/jeu.12522
Subject(s) - naegleria fowleri , biology , blood–brain barrier , in vitro , microbiology and biotechnology , tight junction , immunology , neuroscience , biochemistry , central nervous system , meningoencephalitis
Abstract Naegleria fowleri causes a fatal disease known as primary amoebic meningoencephalitis. This condition is characterized by an acute inflammation that originates from the free passage of peripheral blood cells to the central nervous system through the alteration of the blood–brain barrier. In this work, we established models of the infection in rats and in a primary culture of endothelial cells from rat brains with the aim of evaluating the activation and the alterations of these cells by N. fowleri . We proved that the rat develops the infection similar to the mouse model. We also found that amoebic cysteine proteases produced by the trophozoites and the conditioned medium induced cytopathic effect in the endothelial cells. In addition, N. fowleri can decrease the transendothelial electrical resistance by triggering the destabilization of the tight junction proteins claudin‐5, occludin, and ZO ‐1 in a time‐dependent manner. Furthermore, N. fowleri induced the expression of VCAM ‐1 and ICAM ‐1 and the production of IL ‐8, IL ‐1β, TNF ‐α, and IL ‐6 as well as nitric oxide. We conclude that N. fowleri damaged the blood–brain barrier model by disrupting the intercellular junctions and induced the presence of inflammatory mediators by allowing the access of inflammatory cells to the olfactory bulbs.