scholarly journals The extracellular matrix protein laminin-10 promotes blood–brain barrier repair after hypoxia and inflammation in vitro

2016 ◽  
Vol 13 (1) ◽  
Author(s):  
Korakoch Kangwantas ◽  
Emmanuel Pinteaux ◽  
Jeffrey Penny
2014 ◽  
Vol 34 (46) ◽  
pp. 15260-15280 ◽  
Author(s):  
M. J. Menezes ◽  
F. K. McClenahan ◽  
C. V. Leiton ◽  
A. Aranmolate ◽  
X. Shan ◽  
...  

2013 ◽  
Vol 33 (4) ◽  
pp. 575-582 ◽  
Author(s):  
Quoc Bao Dang ◽  
Bertrand Lapergue ◽  
Alexy Tran-Dinh ◽  
Devy Diallo ◽  
Juan-Antonio Moreno ◽  
...  

Breakdown of the blood–brain barrier (BBB) is a key step associated with ischemic stroke and its increased permeability causes extravasation of plasma proteins and circulating leukocytes. Polymorphonuclear neutrophil (PMN) proteases may participate in BBB breakdown. We investigated the role of PMNs in ischemic conditions by testing their effects on a model of BBB in vitro, under oxygen-glucose deprivation (OGD) to mimic ischemia, supplemented or not with high-density lipoproteins (HDLs) to assess their potential protective effects. Human cerebral endothelial cells cultured on transwells were incubated for 4 hours under OGD conditions with or without PMNs and supplemented or not with HDLs or alpha-1 antitrypsin (AAT, an elastase inhibitor). The integrity of the BBB was then assessed and the effect of HDLs on PMN-induced proteolysis of extracellular matrix proteins was evaluated. The release of myeloperoxidase and matrix metalloproteinase 9 (MMP-9) by PMNs was quantified. Polymorphonuclear neutrophils significantly increased BBB permeability under OGD conditions via proteolysis of extracellular matrix proteins. This was associated with PMN degranulation. Addition of HDLs or AAT limited the proteolysis and associated increased permeability by inhibiting PMN activation. Our results suggest a deleterious, elastase-mediated role of activated PMNs under OGD conditions leading to BBB disruption that could be inhibited by HDLs.


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

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 892
Author(s):  
Elisa L. J. Moya ◽  
Elodie Vandenhaute ◽  
Eleonora Rizzi ◽  
Marie-Christine Boucau ◽  
Johan Hachani ◽  
...  

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.


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

2021 ◽  
Vol 22 (11) ◽  
pp. 5534
Author(s):  
Elin Engdahl ◽  
Maarten van Schijndel ◽  
Dimitrios Voulgaris ◽  
Michela Di Criscio ◽  
Kerry Ramsbottom ◽  
...  

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.


Sign in / Sign up

Export Citation Format

Share Document