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 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 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 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

scholarly journals Miniaturization and Automation of a Human In Vitro Blood–Brain Barrier Model for the High-Throughput Screening of Compounds in the Early Stage of Drug Discovery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Blood Brain Barrier ◽  
Early Stage ◽  
Molecular Transport ◽  
Brain Barrier ◽  
Blood Brain ◽  
Cns Drugs ◽  
The Impact ◽  
The Brain

Central nervous system (CNS) diseases are one of the top causes of death worldwide. As there is a difficulty of drug penetration into the brain due to the blood–brain barrier (BBB), many CNS drugs treatments fail in clinical trials. Hence, there is a need to develop effective CNS drugs following strategies for delivery to the brain by better selecting them as early as possible during the drug discovery process. The use of in vitro BBB models has proved useful to evaluate the impact of drugs/compounds toxicity, BBB permeation rates and molecular transport mechanisms within the brain cells in academic research and early-stage drug discovery. However, these studies that require biological material (animal brain or human cells) are time-consuming and involve costly amounts of materials and plastic wastes due to the format of the models. Hence, to adapt to the high yields needed in early-stage drug discoveries for compound screenings, a patented well-established human in vitro BBB model was miniaturized and automated into a 96-well format. This replicate met all the BBB model reliability criteria to get predictive results, allowing a significant reduction in biological materials, waste and a higher screening capacity for being extensively used during early-stage drug discovery studies.

scholarly journals Low nanogel stiffness favors nanogel transcytosis across an in vitro blood–brain barrier

2021 ◽  
Vol 34 ◽  
pp. 102377
Author(s):  
Laís Ribovski ◽  
Edwin de Jong ◽  
Olga Mergel ◽  
Guangyue Zu ◽  
Damla Keskin ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Bisphenol A Inhibits the Transporter Function of the Blood-Brain Barrier by Directly Interacting with the ABC Transporter Breast Cancer Resistance Protein (BCRP)

2021 ◽  
Vol 22 (11) ◽  
pp. 5534
Author(s):  
Elin Engdahl ◽  
Maarten van Schijndel ◽  
Dimitrios Voulgaris ◽  
Michela Di Criscio ◽  
Kerry Ramsbottom ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bisphenol A ◽  
Blood Brain Barrier ◽  
Breast Cancer Resistance Protein ◽  
Brain Barrier ◽  
Production Volume ◽  
Cancer Resistance ◽  
Blood Brain ◽  
Resistance Protein

The breast cancer resistance protein (BCRP) is an important efflux transporter in the blood-brain barrier (BBB), protecting the brain from a wide range of substances. In this study, we investigated if BCRP function is affected by bisphenol A (BPA), a high production volume chemical used in common consumer products, as well as by bisphenol F (BPF) and bisphenol S (BPS), which are used to substitute BPA. We employed a transwell-based in vitro cell model of iPSC-derived brain microvascular endothelial cells, where BCRP function was assessed by measuring the intracellular accumulation of its substrate Hoechst 33342. Additionally, we used in silico modelling to predict if the bisphenols could directly interact with BCRP. Our results showed that BPA significantly inhibits the transport function of BCRP. Additionally, BPA was predicted to bind to the cavity that is targeted by known BCRP inhibitors. Taken together, our findings demonstrate that BPA inhibits BCRP function in vitro, probably by direct interaction with the transporter. This effect might contribute to BPA’s known impact on neurodevelopment.

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