scholarly journals Biosensor Technology Reveals the Disruption of the Endothelial Barrier Function and the Subsequent Death of Blood Brain Barrier Endothelial Cells to Sodium Azide and Its Gaseous Products

Biosensors ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 41 ◽  
Author(s):  
Dan Kho ◽  
Rebecca Johnson ◽  
Simon O’Carroll ◽  
Catherine Angel ◽  
E. Scott Graham
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Sodium Azide ◽  
Barrier Function ◽  
Brain Barrier ◽  
Endothelial Barrier ◽  
Endothelial Barrier Function ◽  
Biosensor Technology ◽  
Gaseous Products ◽  
Blood Brain

Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes

1994 ◽  
Vol 107 (5) ◽  
pp. 1347-1357 ◽  
Author(s):  
H. Wolburg ◽  
J. Neuhaus ◽  
U. Kniesel ◽  
B. Krauss ◽  
E.M. Schmid ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Tight Junction ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Primary Cultures ◽  
Brain Barrier ◽  
Brain Endothelial Cells ◽  
Blood Brain ◽  
Camp Levels

Tight junctions between endothelial cells of brain capillaries are the most important structural elements of the blood-brain barrier. Cultured brain endothelial cells are known to loose tight junction-dependent blood-brain barrier characteristics such as macromolecular impermeability and high electrical resistance. We have directly analyzed the structure and function of tight junctions in primary cultures of bovine brain endothelial cells using quantitative freeze-fracture electron microscopy, and ion and inulin permeability. The complexity of tight junctions, defined as the number of branch points per unit length of tight junctional strands, decreased 5 hours after culture but thereafter remained almost constant. In contrast, the association of tight junction particles with the cytoplasmic leaflet of the endothelial membrane bilayer (P-face) decreased continuously with a major drop between 16 hours and 24 hours. The complexity of tight junctions could be increased by elevation of intracellular cAMP levels while phorbol esters had the opposite effect. On the other hand, the P-face association of tight junction particles was enhanced by elevation of cAMP levels and by coculture of endothelial cells with astrocytes or exposure to astrocyte-conditioned medium. The latter effect on P-face association was induced by astrocytes but not fibroblasts. Elevation of cAMP levels together with astrocyte-conditioned medium synergistically increased transendothelial electrical resistance and decreased inulin permeability of primary cultures, thus confirming the effects on tight junction structure and barrier function. P-face association of tight junction particles in brain endothelial cells may therefore be a critical feature of blood-brain barrier function that can be specifically modulated by astrocytes and cAMP levels. Our results suggest an important functional role for the cytoplasmic anchorage of tight junction particles for brain endothelial barrier function in particular and probably paracellular permeability in general.

scholarly journals Podocalyxin is required for maintaining blood–brain barrier function during acute inflammation

2019 ◽  
Vol 116 (10) ◽  
pp. 4518-4527 ◽  
Author(s):  
Jessica Cait ◽  
Michael R. Hughes ◽  
Matthew R. Zeglinski ◽  
Allen W. Chan ◽  
Sabrina Osterhof ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Vascular Endothelial Cells ◽  
Umbilical Vein ◽  
Focal Adhesions ◽  
Brain Barrier ◽  
Cortical Actin ◽  
Inflammatory Conditions ◽  
Blood Brain

Podocalyxin (Podxl) is broadly expressed on the luminal face of most blood vessels in adult vertebrates, yet its function on these cells is poorly defined. In the present study, we identified specific functions for Podxl in maintaining endothelial barrier function. Using electrical cell substrate impedance sensing and live imaging, we found that, in the absence of Podxl, human umbilical vein endothelial cells fail to form an efficient barrier when plated on several extracellular matrix substrates. In addition, these monolayers lack adherens junctions and focal adhesions and display a disorganized cortical actin cytoskeleton. Thus, Podxl has a key role in promoting the appropriate endothelial morphogenesis required to form functional barriers. This conclusion is further supported by analyses of mutant mice in which we conditionally deleted a floxed allele ofPodxlin vascular endothelial cells (vECs) using Tie2Cre mice (PodxlΔTie2Cre). Although we did not detect substantially altered permeability in naïve mice, systemic priming with lipopolysaccharide (LPS) selectively disrupted the blood–brain barrier (BBB) inPodxlΔTie2Cremice. To study the potential consequence of this BBB breach, we used a selective agonist (TFLLR-NH2) of the protease-activated receptor-1 (PAR-1), a thrombin receptor expressed by vECs, neuronal cells, and glial cells. In response to systemic administration of TFLLR-NH2, LPS-primedPodxlΔTie2Cremice become completely immobilized for a 5-min period, coinciding with severely dampened neuroelectric activity. We conclude that Podxl expression by CNS tissue vECs is essential for BBB maintenance under inflammatory conditions.

scholarly journals Effects of neuromyelitis optica–IgG at the blood–brain barrier in vitro

2016 ◽  
Vol 4 (1) ◽  
pp. e311 ◽  
Author(s):  
Yukio Takeshita ◽  
Birgit Obermeier ◽  
Anne C. Cotleur ◽  
Simona F. Spampinato ◽  
Fumitaka Shimizu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Neuromyelitis Optica ◽  
Barrier Function ◽  
Brain Barrier ◽  
Chemokine Production ◽  
Leukocyte Transmigration ◽  
Aqp4 Expression ◽  
Blood Brain

Objective:To address the hypothesis that physiologic interactions between astrocytes and endothelial cells (EC) at the blood–brain barrier (BBB) are afflicted by pathogenic inflammatory signaling when astrocytes are exposed to aquaporin-4 (AQP4) antibodies present in the immunoglobulin G (IgG) fraction of serum from patients with neuromyelitis optica (NMO), referred to as NMO-IgG.Methods:We established static and flow-based in vitro BBB models incorporating co-cultures of conditionally immortalized human brain microvascular endothelial cells and human astrocyte cell lines with or without AQP4 expression.Results:In astrocyte–EC co-cultures, exposure of astrocytes to NMO-IgG decreased barrier function, induced CCL2 and CXCL8 expression by EC, and promoted leukocyte migration under flow, contingent on astrocyte expression of AQP4. NMO-IgG selectively induced interleukin (IL)-6 production by AQP4-positive astrocytes. When EC were exposed to IL-6, we observed decreased barrier function, increased CCL2 and CXCL8 expression, and enhanced leukocyte transmigration under flow. These effects were reversed after application of IL–6 neutralizing antibody.Conclusions:Our results indicate that NMO-IgG induces IL-6 production by AQP4-positive astrocytes and that IL-6 signaling to EC decreases barrier function, increases chemokine production, and enhances leukocyte transmigration under flow.

The Blood-Brain Barrier and Blood-Cerebral Spinal Fluid Barrier

2006 ◽  
Vol 10 (2) ◽  
pp. 128-131 ◽  
Author(s):  
Dixon M. Moody
Keyword(s):  
Endothelial Cells ◽  
Cerebrospinal Fluid ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Brain Injuries ◽  
Brain Barrier ◽  
Normal Brain ◽  
Blood Brain ◽  
Clinical Consequences ◽  
The Brain

An intact blood-brain barrier and normal production, circulation, and absorption of cerebrospinal fluid are critical for normal brain function. Minor disruptions of barrier function are without clinical consequences. Major disruptions accompany most significant acute brain injuries. The anatomic location of the blood-brain barrier is the endothelial cells of arterioles, capillaries, veins, and the epithelial cell surface of the choroid plexus. However, endothelial cells require the presence of glial cells to maintain barrier function. During cardiopulmonary bypass, several factors may result in a temporary disruption of the barrier; the most important are systemic inflammatory response and focal ischemia due to emboli. Lacking a lymphatic system, the brain depends on the circulation of cerebrospinal fluid to remove the products of metabolism, and the circulation of cerebrospinal fluid depends on a vascular systolic pulse wave to drive this fluid antegrade along the brain paravascular spaces. Although it is not possible to identify this paravavscular space histologically, its presence is confirmed by tracer methods.

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
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