A novel hypothesis of blood-brain barrier (BBB) development and in vitro BBB model: neural stem cell is the driver of BBB formation and maintenance

2012 ◽  
Vol 2 (1) ◽  
pp. 39 ◽  
Author(s):  
Jian Lu
Keyword(s):  
Stem Cell ◽  
Neural Stem Cell ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
In Vitro Bbb Model

Refining In Vitro Neurotoxicity Testing — The Development of Blood–Brain Barrier Models

2003 ◽  
Vol 31 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Hanna Tähti ◽  
Heidi Nevala ◽  
Tarja Toimela
Keyword(s):  
Blood Brain Barrier ◽  
Cell Lines ◽  
Three Dimensional ◽  
Brain Barrier ◽  
Culture Methods ◽  
Blood Brain ◽  
Capillary Endothelial Cells ◽  
In Vitro Bbb Model

The purpose of this paper is to review the current state of development of advanced in vitro blood–brain barrier (BBB) models. The BBB is a special capillary bed that separates the blood from the central nervous system (CNS) parenchyma. Astrocytes maintain the integrity of the BBB, and, without astrocytic contacts, isolated brain capillary endothelial cells in culture lose their barrier characteristics. Therefore, when developing in vitro BBB models, it is important to add astrocytic factors into the culture system. Recently, novel filter techniques and co-culture methods have made it possible to develop models which resemble the in vivo functions of the BBB in an effective way. With a BBB model, kinetic factors can be added into the in vitro batteries used for evaluating the neurotoxic potential of chemicals. The in vitro BBB model also represents a useful tool for the in vitro prediction of the BBB permeability of drugs, and offers the possibility to scan a large number of drugs for their potential to enter the CNS. Cultured monolayers of brain endothelial cell lines or selected epithelial cell lines, combined with astrocyte and neuron cultures, form a novel three-dimensional technique for the screening of neurotoxic compounds.

scholarly journals VLA-4 mediated adhesion of melanoma cells on the blood–brain barrier is the critical cue for melanoma cell intercalation and barrier disruption

2018 ◽  
Vol 39 (10) ◽  
pp. 1995-2010 ◽  
Author(s):  
Ana B García-Martín ◽  
Pascale Zwicky ◽  
Thomas Gruber ◽  
Christoph Matti ◽  
Federica Moalli ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Blood Brain Barrier ◽  
Barrier Properties ◽  
Melanoma Cells ◽  
Brain Barrier ◽  
Adhesive Interaction ◽  
Inflammatory Conditions ◽  
Blood Brain ◽  
In Vitro Bbb Model

Melanoma is the most aggressive skin cancer in humans. One severe complication is the formation of brain metastasis, which requires extravasation of melanoma cells across the tight blood–brain barrier (BBB). Previously, VLA-4 has been assigned a role for the adhesive interaction of melanoma cells with non-BBB endothelial cells. However, the role of melanoma VLA-4 for breaching the BBB remained unknown. In this study, we used a mouse in vitro BBB model and imaged the shear resistant arrest of melanoma cells on the BBB. Similar to effector T cells, inflammatory conditions of the BBB increased the arrest of melanoma cells followed by a unique post-arrest behavior lacking immediate crawling. However, over time, melanoma cells intercalated into the BBB and compromised its barrier properties. Most importantly, antibody ablation of VLA-4 abrogated melanoma shear resistant arrest on and intercalation into the BBB and protected the BBB from barrier breakdown. A tissue microarray established from human brain metastasis revealed that indeed a majority of 92% of all human melanoma brain metastases stained VLA-4 positive. We propose VLA-4 as a target for the inhibition of brain metastasis formation in the context of personalized medicine identifying metastasizing VLA-4 positive melanoma.

Interferon-β stabilizes barrier characteristics of the blood–brain barrier in four different species in vitro

2008 ◽  
Vol 14 (6) ◽  
pp. 843-852 ◽  
Author(s):  
J Kraus ◽  
K Voigt ◽  
AM Schuller ◽  
M Scholz ◽  
KS Kim ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Treatment Efficacy ◽  
Paracellular Permeability ◽  
Brain Barrier ◽  
Early Event ◽  
Interferon Β ◽  
Recombinant Interferon ◽  
Blood Brain ◽  
In Vitro Bbb Model

Background Blood–brain barrier (BBB) breakdown is an early event in the pathogenesis of multiple sclerosis (MS). In a previous study we have found a direct stabilization of barrier characteristics after treatment of bovine brain capillary endothelial cells (BCECs) with human recombinant interferon-β-1a (IFN-β-1a) in an in vitro BBB model. In the present study we examined the effect of human recombinant IFN-β-1a on the barrier properties of BCECs derived from four different species including humans to predict treatment efficacy of IFN-β-1a in MS patients. Methods We used primary bovine and porcine BCECs, as well as human and murine BCEC cell lines. We investigated the influence of human recombinant IFN-β-1a on the paracellular permeability for 3H-inulin and 14C-sucrose across monolayers of bovine, human, and murine BCECs. In addition, the transendothelial electrical resistance (TEER) was determined in in vitro systems applying porcine and murine BCECS. Results We found a stabilizing effect on the barrier characteristics of BCECs after pretreatment with IFN-β-1a in all applied in vitro models: addition of IFN-β-1a resulted in a significant decrease of the paracellular permeability across monolayers of human, bovine, and murine BCECs. Furthermore, the TEER was significantly increased after pretreatment of porcine and murine BCECs with IFN-β-1a. Conclusion Our data suggest that BBB stabilization by IFN-β-1a may contribute to its beneficial effects in the treatment of MS. A human in vitro BBB model might be useful as bioassay for testing the treatment efficacy of drugs in MS.

scholarly journals ALCAM (CD166) is involved in extravasation of monocytes rather than T cells across the blood–brain barrier

2016 ◽  
Vol 37 (8) ◽  
pp. 2894-2909 ◽  
Author(s):  
Ruth Lyck ◽  
Marc-André Lécuyer ◽  
Michael Abadier ◽  
Christof B Wyss ◽  
Christoph Matti ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Th1 Cells ◽  
Human Brain Tissue ◽  
Autoimmune Encephalomyelitis ◽  
Tissue Samples ◽  
Blood Brain ◽  
Static Conditions ◽  
In Vitro Bbb Model

Activated leukocyte cell adhesion molecule (ALCAM) has been proposed to mediate leukocyte migration across the blood–brain barrier (BBB) in multiple sclerosis or experimental autoimmune encephalomyelitis (EAE). Here, we confirmed vascular ALCAM expression in human brain tissue samples in situ and on two different human in vitro BBB models. Antibody-mediated inhibition of ALCAM reduced diapedesis of human CD4+ Th1 but not of Th17 cells across the human BBB in vitro. In accordance to human Th1 cells, mouse Th1 cells showed reduced diapedesis across an ALCAM−/− in vitro BBB model under static but no longer under flow conditions. In contrast to the limited role of ALCAM in T cell extravasation across the BBB, we found a contribution of ALCAM to rolling, adhesion, and diapedesis of human CD14+ monocytes across the human BBB under flow and static conditions. Taken together, our study highlights the potential differences in the CNS expression of ALCAM in mouse and human and supports a prominent role for ALCAM in the multi-step extravasation of monocytes across the BBB.

scholarly journals Cellular Prion Protein Participates in Amyloid-β Transcytosis across the Blood—Brain Barrier

2012 ◽  
Vol 32 (4) ◽  
pp. 628-632 ◽  
Author(s):  
Thorsten Pflanzner ◽  
Benjamin Petsch ◽  
Bettina André-Dohmen ◽  
Andreas Müller-Schiffmann ◽  
Sabrina Tschickardt ◽  
...  
Keyword(s):  
Prion Protein ◽  
Blood Brain Barrier ◽  
Amyloid Β ◽  
Cellular Prion Protein ◽  
Brain Barrier ◽  
Putative Receptor ◽  
Blood Brain ◽  
In Vitro Bbb Model

The blood—brain barrier (BBB) facilitates amyloid-β (Aβ) exchange between the blood and the brain. Here, we found that the cellular prion protein (PrPc), a putative receptor implicated in mediating Aβ neurotoxicity in Alzheimer's disease (AD), participates in Aβ transcytosis across the BBB. Using an in vitro BBB model, [125I]-Aβ1–40 transcytosis was reduced by genetic knockout of PrPc or after addition of a competing PrPc-specific antibody. Furthermore, we provide evidence that PrPc is expressed in endothelial cells and, that monomeric Aβ1–40 binds to PrPc. These observations provide new mechanistic insights into the role of PrPc in AD.

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