Corrigendum to “Blood-brain barrier function, cell viability, and gene expression of tight junction-associated proteins in the mouse are disrupted by crude oil, benzo[a]pyrene, and the dispersant COREXIT” [Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 223 (2019); 96–105]

2020 ◽  
Vol 228 ◽  
pp. 108675
Author(s):  
Dao H. Ho ◽  
Warren W. Burggren
Keyword(s):  
Gene Expression ◽  
Tight Junction ◽  
Cell Viability ◽  
Crude Oil ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Brain Barrier ◽  
Blood Brain ◽  
Associated Proteins ◽  
Function Cell

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 Human Brain Endothelial CXCR2 is Inflammation-Inducible and Mediates CXCL5- and CXCL8-Triggered Paraendothelial Barrier Breakdown

2019 ◽  
Vol 20 (3) ◽  
pp. 602 ◽  
Author(s):  
Axel Haarmann ◽  
Michael Schuhmann ◽  
Christine Silwedel ◽  
Camelia-Maria Monoranu ◽  
Guido Stoll ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Tight Junction ◽  
Human Brain ◽  
Blood Brain Barrier ◽  
Barrier Function ◽  
Morphological Changes ◽  
Brain Barrier ◽  
Microvascular Endothelial Cell ◽  
Inflammatory Conditions ◽  
Blood Brain

Chemokines (C-X-C) motif ligand (CXCL) 5 and 8 are overexpressed in patients with multiple sclerosis, where CXCL5 serum levels were shown to correlate with blood–brain barrier dysfunction as evidenced by gadolinium-enhanced magnetic resonance imaging. Here, we studied the potential role of CXCL5/CXCL8 receptor 2 (CXCR2) as a regulator of paraendothelial brain barrier function, using the well-characterized human cerebral microvascular endothelial cell line hCMEC/D3. Low basal CXCR2 mRNA and protein expression levels in hCMEC/D3 were found to strongly increase under inflammatory conditions. Correspondingly, immunohistochemistry of brain biopsies from two patients with active multiple sclerosis revealed upregulation of endothelial CXCR2 compared to healthy control tissue. Recombinant CXCL5 or CXCL8 rapidly and transiently activated Akt/protein kinase B in hCMEC/D3. This was followed by a redistribution of tight junction-associated protein zonula occludens-1 (ZO-1) and by the formation of actin stress fibers. Functionally, these morphological changes corresponded to a decrease of paracellular barrier function, as measured by a real-time electrical impedance-sensing system. Importantly, preincubation with the selective CXCR2 antagonist SB332235 partially prevented chemokine-induced disturbance of both tight junction morphology and function. We conclude that human brain endothelial CXCR2 may contribute to blood–brain barrier disturbance under inflammatory conditions with increased CXCL5 and CXCL8 expression, where CXCR2 may also represent a novel pharmacological target for blood–brain barrier stabilization.

Abstract T P250: Role of Autophagy in Blood-Brain Barrier Disruption and Tight Junction Degradation Under Ischemic Condition

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kyeong-A Kim ◽  
Young-Jun Shin ◽  
Eun-Sun Kim ◽  
Muhammad Akram ◽  
Dabi Noh ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Tight Junction ◽  
Cell Viability ◽  
Blood Brain Barrier ◽  
Neuronal Damage ◽  
Cell Damage ◽  
Brain Barrier ◽  
Blood Brain ◽  
Junction Protein

During ischemic stroke, the integrity of blood-brain barrier (BBB), which shows selective permeability for substances to brain, is significantly damaged amplifying ischemic neuronal damage. There have been attempts to identify the exact mechanism ischemic BBB disruption to minimize brain damage under ischemic stroke. Autophagy is catabolic process which involves degradation and recycling of damaged or unnecessary organelles. However, excessive autophagy can induce cell damage and death under pathological conditions such as ischemia. In this study, we evaluated if autophagy is a key mechanism of BBB dysfunction under ischemic stroke. In vitro BBB model of bEnd.3 cells were exposed to oxygen-glucose deprivation (OGD), an ischemic mimic condition. After exposure to OGD for 18 hours, cell viability was significantly decreased and cellular permeability was impaired. The conversion of LC3-I to LC3-II and puncta of LC3 in bEnd.3 were increased, demonstrating that autophagy is induced under ischemic condition. Modulation of autophagy by 3-methyladenine, an autophagy inhibitor, reversed the conversion of LC3 as well as decreased cell viability, suggesting that autophagy involves in ischemic BBB damage. The level of occludin, a tight junction protein in BBB, was decreased after OGD, and this was reversed by inhibition of autophagy. Our findings showed that induction of autophagy might contribute to increased permeability through occludin degradation in brain endothelial cells under ischemia, providing a new mechanism of BBB disruption in ischemic stroke.

scholarly journals Claudin-12 is not required for blood–brain barrier tight junction function

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Mariana Castro Dias ◽  
◽  
Caroline Coisne ◽  
Pascale Baden ◽  
Gaby Enzmann ◽  
...  
Keyword(s):  
Tight Junction ◽  
Blood Brain Barrier ◽  
Cell Types ◽  
Brain Barrier ◽  
Blood Brain ◽  
Exact Function ◽  
Associated Proteins ◽  
Junctional Complexes ◽  
Paracellular Diffusion ◽  
Cardiovascular Functions

Abstract Background The blood–brain barrier (BBB) ensures central nervous system (CNS) homeostasis by strictly controlling the passage of molecules and solutes from the bloodstream into the CNS. Complex and continuous tight junctions (TJs) between brain endothelial cells block uncontrolled paracellular diffusion of molecules across the BBB, with claudin-5 being its dominant TJs protein. However, claudin-5 deficient mice still display ultrastructurally normal TJs, suggesting the contribution of other claudins or tight-junction associated proteins in establishing BBB junctional complexes. Expression of claudin-12 at the BBB has been reported, however the exact function and subcellular localization of this atypical claudin remains unknown. Methods We created claudin-12-lacZ-knock-in C57BL/6J mice to explore expression of claudin-12 and its role in establishing BBB TJs function during health and neuroinflammation. We furthermore performed a broad standardized phenotypic check-up of the mouse mutant. Results Making use of the lacZ reporter allele, we found claudin-12 to be broadly expressed in numerous organs. In the CNS, expression of claudin-12 was detected in many cell types with very low expression in brain endothelium. Claudin-12lacZ/lacZ C57BL/6J mice lacking claudin-12 expression displayed an intact BBB and did not show any signs of BBB dysfunction or aggravated neuroinflammation in an animal model for multiple sclerosis. Determining the precise localization of claudin-12 at the BBB was prohibited by the fact that available anti-claudin-12 antibodies showed comparable detection and staining patterns in tissues from wild-type and claudin-12lacZ/lacZ C57BL/6J mice. Conclusions Our present study thus shows that claudin-12 is not essential in establishing or maintaining BBB TJs integrity. Claudin-12 is rather expressed in cells that typically lack TJs suggesting that claudin-12 plays a role other than forming classical TJs. At the same time, in depth phenotypic screening of clinically relevant organ functions of claudin-12lacZ/lacZ C57BL/6J mice suggested the involvement of claudin-12 in some neurological but, more prominently, in cardiovascular functions.

scholarly journals Glucocorticoid effects on endothelial barrier function in the murine brain endothelial cell line cEND incubated with sera from patients with multiple sclerosis

2010 ◽  
Vol 16 (3) ◽  
pp. 293-302 ◽  
Author(s):  
Kinga G Blecharz ◽  
Aiden Haghikia ◽  
Mariusz Stasiolek ◽  
Niels Kruse ◽  
Detlev Drenckhahn ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Endothelial Cell ◽  
Tight Junction ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Junction Protein ◽  
Blood Brain Barrier Integrity

Compromised blood—brain barrier integrity is a major hallmark of active multiple sclerosis (MS). Alterations in brain endothelial tight junction protein and gene expression occur early during neuroinflammation but there is little known about the underlying mechanisms. In this study, we analysed barrier compromising effects of sera from MS patients and barrier restoring effects of glucocorticoids on blood—brain barrier integrity in vitro. cEND murine brain microvascular endothelial cell monolayers were incubated with sera from patients in active phase of disease or in relapse. Data were compared with effects of the glucocorticoid dexamethasone alone or in combination with MS sera on barrier integrity. Tight junction protein levels and gene expression were evaluated concomitant with barrier integrity. We reveal downregulation of claudin-5 and occludin protein and mRNA and an accompanying upregulation in expression of matrix metalloproteinase MMP-9 after incubation with serum from active disease and remission and also a minor reconstitution of barrier functions related to dexamethasone treatment. Moreover, we for the first time describe downregulation of claudin-5 and occludin protein after incubation of cEND cells with sera from patients in remission phase of MS. Our findings reveal direct and differential effects of MS sera on blood-brain barrier integrity.

Sign in / Sign up

Export Citation Format

Share Document