scholarly journals Transport of Glial Cell Line-Derived Neurotrophic Factor into Liposomes across the Blood-Brain Barrier: In Vitro and in Vivo Studies

2014 ◽  
Vol 15 (3) ◽  
pp. 3612-3623 ◽  
Author(s):  
Shaoling Wu ◽  
Guoqi Li ◽  
Xiao Li ◽  
Caina Lin ◽  
Ding Yu ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Brain Barrier ◽  
In Vivo Studies ◽  
Blood Brain

scholarly journals EXTH-66. NEO100 TRANSIENTLY OPENS UP THE BLOOD BRAIN BARRIER VIA TIGHT JUNCTION INHIBITION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii101-ii102
Author(s):  
Thomas Chen ◽  
Weijun Wang ◽  
Nagore Marin Ramos ◽  
Axel Schonthal
Keyword(s):  
Tight Junction ◽  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
In Vivo Studies ◽  
Blue Dye ◽  
Blood Brain ◽  
Main Technique

Abstract The blood brain barrier (BBB) prevents effective entry of nearly all therapeutics to the central nervous system (CNS), preventing effective treatment of brain-related malignancies. Intracarotid mannitol injection has been the main technique to transiently open up the BBB, with its attendant variability and complications. A more direct and better tolerated method is needed to open up the BBB. We present our discovery that intraarterial (IA) injection of NEO100, a cGMP-quality form of perillyl alcohol (POH), transiently opens up the BBB in a safe and reversible manner. We used in-vitro models of MDCK1 and patient derived brain endothelial cell (BEC) + astrocyte barriers to determine that NEO100 increased FITC-antibody diffusion across the in-vitro BBB model and decreased trans-epithelial/endothelial electrical resistance (TEER). NEO100 effects on transcellular and paracellular pathways were studied using western blot, flow cytometry, HPLC, fluorescent probes, microarray analysis, and transmission electron microscopy. In-vivo studies were performed using ultrasound-guided intracardiac administration of NEO100 in mice with subsequent intravenous delivery of non-BBB permeable therapeutic agents. We determined that NEO100 transiently disrupts the transcellular pathway by permeabilizing BEC membranes, and the paracellular pathway via delocalization of tight junction proteins. In vivo IA NEO100 administration caused an effective dose- and time-dependent BBB permeabilization, which was reversible and well tolerated by the mice. This was evidenced by the spreading of Evans blue dye, and of therapeutics with different molecular weights, ie methotrexate, anti-PD-1 antibody, and CAR-T cells in the brain. Our results demonstrate that IA NEO100 is able to open the BBB in a controlled and reversible manner, allowing it to facilitate drug delivery to the CNS.

Pericyte-derived Glial Cell Line-derived Neurotrophic Factor Increase the Expression of Claudin-5 in the Blood–brain Barrier and the Blood-nerve Barrier

2011 ◽  
Vol 37 (2) ◽  
pp. 401-409 ◽  
Author(s):  
Fumitaka Shimizu ◽  
Yasuteru Sano ◽  
Kazuyuki Saito ◽  
Masa-aki Abe ◽  
Toshihiko Maeda ◽  
...  
Keyword(s):  
Cell Line ◽  
Glial Cell ◽  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Modulation of blood–brain barrier permeability by neutrophils: in vitro and in vivo studies

2009 ◽  
Vol 1298 ◽  
pp. 13-23 ◽  
Author(s):  
Shannon L. Joice ◽  
Firdaus Mydeen ◽  
Pierre-Olivier Couraud ◽  
Babette B. Weksler ◽  
Ignacio A. Romero ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
In Vivo Studies ◽  
Barrier Permeability ◽  
Blood Brain Barrier Permeability ◽  
Blood Brain ◽  
Brain Barrier Permeability

Glial Cell Line-Derived Neurotrophic Factor Induces Barrier Function of Endothelial Cells Forming the Blood–Brain Barrier

1999 ◽  
Vol 261 (1) ◽  
pp. 108-112 ◽  
Author(s):  
Yo Igarashi ◽  
Hiroyuki Utsumi ◽  
Hideki Chiba ◽  
Yumiko Yamada-Sasamori ◽  
Hirotoshi Tobioka ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Line ◽  
Glial Cell ◽  
Blood Brain Barrier ◽  
Neurotrophic Factor ◽  
Barrier Function ◽  
Brain Barrier ◽  
Blood Brain

An immortalised astrocyte cell line maintains the in vivo phenotype of a primary porcine in vitro blood–brain barrier model

2012 ◽  
Vol 1479 ◽  
pp. 17-30 ◽  
Author(s):  
Carina A. Cantrill ◽  
Robert A. Skinner ◽  
Nancy J. Rothwell ◽  
Jeffrey I. Penny
Keyword(s):  
Cell Line ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Blood Brain Barrier Model ◽  
Barrier Model

In Vitro and in Vivo Studies on the Transport of PEGylated Silica Nanoparticles across the Blood–Brain Barrier

2014 ◽  
Vol 6 (3) ◽  
pp. 2131-2136 ◽  
Author(s):  
Dan Liu ◽  
Bingqian Lin ◽  
Wei Shao ◽  
Zhi Zhu ◽  
Tianhai Ji ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
In Vivo Studies ◽  
Blood Brain

scholarly journals Analysis of L-leucine amino acid transporter species activity and gene expression by human blood brain barrier hCMEC/D3 model reveal potential LAT1, LAT4, B0AT2 and y+LAT1 functional cooperation

2021 ◽  
pp. 0271678X2110395
Author(s):  
Mehdi Taslimifar ◽  
Martin Faltys ◽  
Vartan Kurtcuoglu ◽  
François Verrey ◽  
Victoria Makrides
Keyword(s):  
Amino Acid ◽  
Blood Brain Barrier ◽  
Cell Model ◽  
Cell Types ◽  
Brain Barrier ◽  
In Vivo Studies ◽  
Amino Acid Transporters ◽  
Blood Brain

In the CNS, amino acid (AA) neurotransmitters and neurotransmitter precursors are subject to tight homeostatic control mediated by blood-brain barrier (BBB) solute carrier amino acid transporters (AATs). Since the BBB is composed of multiple closely apposed cell types and opportunities for human in vivo studies are limited, we used in vitro and computational approaches to investigate human BBB AAT activity and regulation. Quantitative real-time PCR (qPCR) of the human BBB endothelial cell model hCMEC/D3 (D3) was used to determine expression of selected AAT, tight junction (TJ), and signal transduction (ST) genes under various culture conditions. L-leucine uptake data were interrogated with a computational model developed by our group for calculating AAT activity in complex cell cultures. This approach is potentially applicable to in vitro cell culture drug studies where multiple “receptors” may mediate observed responses. Of 7 Leu AAT genes expressed by D3 only the activity of SLC7A5-SLC3A2/LAT1-4F2HC (LAT1), SLC43A2/LAT4 (LAT4) and sodium-dependent AATs, SLC6A15/B0AT2 (B0AT2), and SLC7A7/y+LAT1 (y+LAT1) were calculated to be required for Leu uptake. Therefore, D3 Leu transport may be mediated by a potentially physiologically relevant functional cooperation between the known BBB AAT, LAT1 and obligatory exchange (y+LAT1), facilitative diffusion (LAT4), and sodium symporter (B0AT2) transporters.

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