scholarly journals Immortalized Human Brain Endothelial Cell Line HCMEC/D3 as a Model of the Blood-Brain Barrier Facilitates In Vitro Studies of Central Nervous System Infection by Cryptococcus neoformans

2009 ◽  
Vol 8 (11) ◽  
pp. 1803-1807 ◽  
Author(s):  
Kiem Vu ◽  
Babette Weksler ◽  
Ignacio Romero ◽  
Pierre-Olivier Couraud ◽  
Angie Gelli
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Endothelial Cell ◽  
Human Brain ◽  
Cell Line ◽  
Blood Brain Barrier ◽  
Central Nervous System Infection ◽  
Brain Barrier ◽  
Brain Endothelial Cell ◽  
Blood Brain

ABSTRACT Cryptococcus neoformans cells must cross the blood-brain barrier prior to invading the central nervous system. Here we demonstrate that the immortalized human brain endothelial cell line HCMEC/D3 is a useful alternative to primary brain endothelial cells as a model of the blood-brain barrier for studies of central nervous system infection.

Anti-Tumor Effect of INNO-406, a Novel Bcr-Abl Inhibitor in Combination with Cyclosporin A Against the Murine Central Nervous System and Systemic Leukemia Model.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1598-1598
Author(s):  
Asumi Yokota ◽  
Shinya Kimura ◽  
Satohiro Masuda ◽  
Eishi Ashihara ◽  
Yoshimasa Urasaki ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Plasma Concentration ◽  
Cyclosporin A ◽  
Cell Line ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Cancer Center ◽  
Combination Effect ◽  
Blood Brain

Abstract Central nervous system (CNS) is one of the major cites for extramedullary relapse of Ph+ leukemias, which have been treated with imatinib mesylate (IM). The reason for this is that IM is a substrate for P-glycoprotein (P-gp) at the blood brain barrier and effluxed by it. We have already shown in the last annual meeting that INNO-406 had much stronger anti-tumor effects against the murine CNS leukemia model compared with IM, and INNO-406 is also effluxed from the murine CNS by P-gp. In this study, we investigated the combination effect of INNO-406 and P-gp inhibitors, verapamil or cyclosporin-A (CsA). First, we examined the growth-suppressive effect of INNO-406 and the combination with the P-gp inhibitors against the BCR-ABL positive leukemic cell line, K562 and the P-gp-overexpressing K562, K562/D1-9 cell line. K562/D1-9 showed 10 times higher resistant to both IM and INNO-406 compared with K562. Furthermore, both verapamil and CsA synergistically augmented the effect of INNO-406. Next, we investigated the pharmacokinetics of INNO-406 when orally administrated with CsA to mice. Mice were administrated p.o. with 50mg/kg of CsA 2 hours before INNO-406. We found that the concentration of INNO-406 in the CNS elevated by 2 times when combined with CsA, while the plasma concentration was decreased to two thirds of that when singly administrated with INNO-406. It was suggested that the decreased plasma concentration of INNO-406 seen here resulted from the increased uptake into the CNS by CsA inhibiting P-gp at the blood brain barrier. These changes of the drug distribution to the murine tissues may alter the anti-leukemic effect of INNO-406, thus we planned to investigate the combination effect of INNO-406 and CsA in the murine models of both CNS and systemic leukemia. We found that CsA significantly augmented the anti-tumor effect of INNO-406 in the CNS leukemia model. Moreover, in spite of the decreased plasma concentration of INNO-406, the combination with CsA also prolonged the survival phase of the mice in the systemic leukemia model, more significantly than single treatment of INNO-406 (Figure). This may be explained by which CsA increased the intracellular uptake of INNO-406, resulted from the direct inhibition of drug efflux via P-gp expressed in the leukemic cells. Phase I clinical study on INNO-406 is now underway in MD Anderson Cancer Center and in Frankfurt University. From the results of this study, we expected the effective application of INNO-406 in combination with P-gp inhibitor to the patients suffering from refractory Ph+ leukemia as well as CNS relapse. Figure Figure

scholarly journals Blood‐brain barrier‐specific properties of a human adult brain endothelial cell line

2005 ◽  
Vol 19 (13) ◽  
pp. 1872-1874 ◽  
Author(s):  
B. B. Weksler ◽  
E. A. Subileau ◽  
N. Perrière ◽  
P. Charneau ◽  
K. Holloway ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Line ◽  
Blood Brain Barrier ◽  
Adult Brain ◽  
Brain Barrier ◽  
Brain Endothelial Cell ◽  
Endothelial Cell Line ◽  
Human Adult ◽  
Blood Brain

scholarly journals Central nervous system delivery of molecules across the blood-brain barrier

2021 ◽  
pp. 104952
Author(s):  
Fabien Gosselet ◽  
Rodrigo Azevedo Loiola ◽  
Anna Roig ◽  
Anna Rosell ◽  
Maxime Culot
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Brain Endothelial Cell-Cell Junctions: How to “Open” the Blood Brain Barrier

2008 ◽  
Vol 6 (3) ◽  
pp. 179-192 ◽  
Author(s):  
Svetlana Stamatovic ◽  
Richard Keep ◽  
Anuska Andjelkovic
Keyword(s):  
Endothelial Cell ◽  
Blood Brain Barrier ◽  
Cell Junctions ◽  
Brain Barrier ◽  
Brain Endothelial Cell ◽  
Blood Brain ◽  
Cell Cell
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