scholarly journals Protective Effects of Complement Component 8 Gamma Against Blood-Brain Barrier Breakdown

2021 ◽  
Vol 12 ◽  
Author(s):  
Jong-Heon Kim ◽  
Jin Han ◽  
Kyoungho Suk
Keyword(s):  
Blood Brain Barrier ◽  
Neutrophil Infiltration ◽  
Complement Component ◽  
Brain Barrier ◽  
Protective Effects ◽  
Inflammatory Conditions ◽  
Blood Brain ◽  
Sphingosine 1 Phosphate ◽  
Endothelial Integrity

The blood-brain barrier (BBB) regulates the traffic of micromolecules and macromolecules between the peripheral blood and the central nervous system, to maintain brain homeostasis. BBB disruption and dysfunction accompany a variety of neurological disorders and are closely related with the neuroinflammatory cascades that are triggered by leukocyte infiltration and glial activation. Here, we explored the role of complement component 8 gamma (C8G) in the maintenance of BBB integrity. Previously, C8G was shown to inhibit neuroinflammation by interfering with the sphingosine-1-phosphate (S1P)-S1PR2 interaction. The results of the present study revealed that C8G is localized in perivascular astrocytes, whereas S1PR2 is expressed in endothelial cells (ECs). In the lipopolysaccharide (LPS)-induced neuroinflammation model, the intracerebroventricular administration of the recombinant C8G protein protected the integrity of the BBB, whereas shRNA-mediated C8G knockdown enhanced BBB permeability and neutrophil infiltration. Using pharmacological agonists and antagonists of S1PR2, we demonstrated that C8G inhibited the inflammatory activation of ECs in culture by antagonizing S1PR2. In the in vitro BBB model, the addition of the recombinant C8G protein preserved endothelial integrity, whereas the knockdown of C8G exacerbated endothelial leakage under inflammatory conditions. Together, our findings indicate an important role for astrocytic C8G in protecting the BBB in the inflamed brain, suggesting a novel mechanism of cross talk between astrocytes and ECs in terms of BBB maintenance.

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.

scholarly journals Fingolimod (FTY720-P) Does Not Stabilize the Blood–Brain Barrier under Inflammatory Conditions in an in Vitro Model

2015 ◽  
Vol 16 (12) ◽  
pp. 29454-29466 ◽  
Author(s):  
Michael Schuhmann ◽  
Stefan Bittner ◽  
Sven Meuth ◽  
Christoph Kleinschnitz ◽  
Felix Fluri
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Model ◽  
Brain Barrier ◽  
Inflammatory Conditions ◽  
Blood Brain ◽  
Vitro Model

scholarly journals Microbiome–host systems interactions: Protective effects of propionate upon the blood–brain barrier

2017 ◽  
Author(s):  
Lesley Hoyles ◽  
Tom Snelling ◽  
Umm-Kulthum Umlai ◽  
Jeremy K. Nicholson ◽  
Simon R. Carding ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Protective Effects ◽  
Microbial Metabolites ◽  
Blood Brain ◽  
Microbial Infections ◽  
Pathway Regulation ◽  
And Function ◽  
The Impact

AbstractBackgroundGut microbiota composition and function are symbiotically linked with host health, and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognized mechanisms exist by which the microbiome influences the gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesized interactions between circulating gut–derived microbial metabolites and the blood–brain barrier (BBB) also contribute to the gut–brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed.ResultsAfter demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 μM) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signaling.ConclusionsTogether, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut–brain axis that warrants further attention.

scholarly journals Increased Transendothelial Transport of CCL3 Is Insufficient to Drive Immune Cell Transmigration through the Blood–Brain Barrier under Inflammatory Conditions In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Maxime De Laere ◽  
Carmelita Sousa ◽  
Megha Meena ◽  
Roeland Buckinx ◽  
Jean-Pierre Timmermans ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Immune Cell ◽  
Brain Barrier ◽  
Cell Infiltration ◽  
Microvascular Endothelial Cell ◽  
Immune Cell Infiltration ◽  
Cell Trafficking ◽  
Inflammatory Conditions ◽  
Blood Brain

Many neuroinflammatory diseases are characterized by massive immune cell infiltration into the central nervous system. Identifying the underlying mechanisms could aid in the development of therapeutic strategies specifically interfering with inflammatory cell trafficking. To achieve this, we implemented and validated a blood–brain barrier (BBB) model to study chemokine secretion, chemokine transport, and leukocyte trafficking in vitro. In a coculture model consisting of a human cerebral microvascular endothelial cell line and human astrocytes, proinflammatory stimulation downregulated the expression of tight junction proteins, while the expression of adhesion molecules and chemokines was upregulated. Moreover, chemokine transport across BBB cocultures was upregulated, as evidenced by a significantly increased concentration of the inflammatory chemokine CCL3 at the luminal side following proinflammatory stimulation. CCL3 transport occurred independently of the chemokine receptors CCR1 and CCR5, albeit that migrated cells displayed increased expression of CCR1 and CCR5. However, overall leukocyte transmigration was reduced in inflammatory conditions, although higher numbers of leukocytes adhered to activated endothelial cells. Altogether, our findings demonstrate that prominent barrier activation following proinflammatory stimulation is insufficient to drive immune cell recruitment, suggesting that additional traffic cues are crucial to mediate the increased immune cell infiltration seen in vivo during neuroinflammation.

scholarly journals Protective Effects of Folic Acid and Vitamin C Against Iron Overload at the in vitro Blood-Brain Barrier

2021 ◽  
Author(s):  
Belkis ATASEVER ARSLAN ◽  
Enes Furkan ARSLAN ◽  
İdil SATICI ◽  
Ayşegül YANIK ◽  
Seda KUŞOĞLU GÜLTEKİN
Keyword(s):  
Folic Acid ◽  
Vitamin C ◽  
Iron Overload ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Protective Effects ◽  
Blood Brain

scholarly journals Biochemical‐ and Biophysical‐Induced Barriergenesis in the Blood–Brain Barrier: A Review of Barriergenic Factors for Use in In Vitro Models

2021 ◽  
Vol 1 (5) ◽  
pp. 2170051
Author(s):  
Christina L. Schofield ◽  
Aleixandre Rodrigo-Navarro ◽  
Matthew J. Dalby ◽  
Tom Van Agtmael ◽  
Manuel Salmeron-Sanchez
Keyword(s):  
Blood Brain Barrier ◽  
In Vitro Models ◽  
Brain Barrier ◽  
Blood Brain
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