Defective Function of the Blood–Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model

Author(s):  
Shinsuke Nakagawa ◽  
Hiroki Ohara ◽  
Masami Niwa ◽  
Kazuo Yamagata ◽  
Toru Nabika
2000 ◽  
Vol 21 ◽  
pp. 86
Author(s):  
Siobhan M. Brennan ◽  
Lawrence T. McGrath ◽  
Stephen P. McIlroy ◽  
Peter A. Passmore

2006 ◽  
Vol 109 (3-4) ◽  
pp. 233-244 ◽  
Author(s):  
Nicola F. Fletcher ◽  
David J. Brayden ◽  
Brenda Brankin ◽  
Sheila Worrall ◽  
John J. Callanan

2004 ◽  
Vol 998 (2) ◽  
pp. 218-229 ◽  
Author(s):  
Victoria I. Inglis ◽  
Michael P.J. Jones ◽  
Arthur D.Y. Tse ◽  
Alexander S. Easton

2008 ◽  
Vol 97 (12) ◽  
pp. 5158-5175 ◽  
Author(s):  
Winfried Neuhaus ◽  
Verena E. Plattner ◽  
Michael Wirth ◽  
Bettina Germann ◽  
Bodo Lachmann ◽  
...  

1991 ◽  
Vol 115 (6) ◽  
pp. 1725-1735 ◽  
Author(s):  
L L Rubin ◽  
D E Hall ◽  
S Porter ◽  
K Barbu ◽  
C Cannon ◽  
...  

Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.


Pathogens ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Donghoon Kang ◽  
Natalia V. Kirienko

Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that utilizes a wide-range of virulence factors to cause acute, life-threatening infections in immunocompromised patients, especially those in intensive care units. It also causes debilitating chronic infections that shorten lives and worsen the quality of life for cystic fibrosis patients. One of the key virulence factors in P. aeruginosa is the siderophore pyoverdine, which provides the pathogen with iron during infection, regulates the production of secreted toxins, and disrupts host iron and mitochondrial homeostasis. These roles have been characterized in model organisms such as Caenorhabditis elegans and mice. However, an intermediary system, using cell culture to investigate the activity of this siderophore has been absent. In this report, we describe such a system, using murine macrophages treated with pyoverdine. We demonstrate that pyoverdine-rich filtrates from P. aeruginosa exhibit substantial cytotoxicity, and that the inhibition of pyoverdine production (genetic or chemical) is sufficient to mitigate virulence. Furthermore, consistent with previous observations made in C. elegans, pyoverdine translocates into cells and disrupts host mitochondrial homeostasis. Most importantly, we observe a strong correlation between pyoverdine production and virulence in P. aeruginosa clinical isolates, confirming pyoverdine’s value as a promising target for therapeutic intervention. This in vitro cell culture model will allow rapid validation of pyoverdine antivirulents in a simple but physiologically relevant manner.


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