scholarly journals Recent Progress in Microfluidic Models of the Blood-Brain Barrier

Micromachines ◽  
2019 ◽  
Vol 10 (6) ◽  
pp. 375 ◽  
Author(s):  
Lili Jiang ◽  
Shu Li ◽  
Junsong Zheng ◽  
Yan Li ◽  
Hui Huang
Keyword(s):  
Blood Brain Barrier ◽  
Pharmaceutical Research ◽  
Experimental Models ◽  
Brain Barrier ◽  
Design Parameters ◽  
Tight Junction Formation ◽  
Blood Brain ◽  
Micrometer Scale ◽  
Physical And Chemical

The blood-brain barrier (BBB) is a critical physical and chemical barrier that maintains brain homeostasis. Researchers in academia and industry are highly motivated to develop experimental models that can accurately mimic the physiological characteristics of the BBB. Microfluidic systems, which manipulate fluids at the micrometer scale, are ideal tools for simulating the BBB microenvironment. In this review, we summarized the progress in the design and evaluation of microfluidic in vitro BBB models, including advances in chip materials, porous membranes, the use of endothelial cells, the importance of shear stress, the detection specific markers to monitor tight junction formation and integrity, measurements of TEER and permeability. We also pointed out several shortcomings of the current microfluidic models. The purpose of this paper is to let the readers understand the characteristics of different types of model design, and select appropriate design parameters according to the research needs, so as to obtain the best experimental results. We believe that the microfluidics BBB models will play an important role in neuroscience and pharmaceutical research.

scholarly journals Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2843
Author(s):  
Stefan Saretz ◽  
Gabriele Basset ◽  
Liridona Useini ◽  
Markus Laube ◽  
Jens Pietzsch ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Pharmaceutical Research ◽  
Amyloid Β ◽  
Brain Barrier ◽  
Blood Brain ◽  
Secretase Activity ◽  
Number Of Patients ◽  
Aging Populations ◽  
A Cell

All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.

Effects of Chlorpyrifos Exposure on Acetylcholine Metabolism across a Model Blood-Brain Barrier

2019 ◽  
Vol MA2019-02 (55) ◽  
pp. 2426-2426
Author(s):  
Ethan S. McClain ◽  
Dusty R. Miller ◽  
Jacquelyn A Brown ◽  
John P Wikswo ◽  
David E. Cliffel
Keyword(s):  
Blood Brain Barrier ◽  
Neurovascular Unit ◽  
Acetylcholinesterase Activity ◽  
Cell Types ◽  
Electrochemical Analysis ◽  
Brain Barrier ◽  
Agricultural Industry ◽  
Tight Junction Formation ◽  
Blood Brain

Organophosphate (OP) compounds, used throughout the agricultural industry as insecticides, are known to directly and irreparably alter brain function in humans. Exposure to OPs decreases acetylcholinesterase activity and leads to a buildup of acetylcholine, with chronic exposure to sub-lethal levels inducing neuropathy. This buildup of acetylcholine can be monitored through electrochemical methods to study the effects of OP toxicity. The microclinical analyzer (µCA), an in vitro microfluidic device allowing for electrochemical analysis using a screen-printed electrode, can be modified with enzymes to detect acetylcholine. Using the µCA in combination with the neurovascular unit (NVU), an organotypic model of the blood-brain barrier (BBB), can provide a better understanding of the BBB forms, functions, and responds to insults. The NVU supports all the cell types necessary for proper BBB formation (endothelial cells, astrocytes, pericytes, and neurons) and provides the flow-created shear forces for mature tight junction formation. The µCA and NVU were used study the effects of chlorpyrifos on acetylcholine concentrations present across the BBB. Understanding the effects of OP like chlorpyrifos on neurotoxicity can contributes to the assessment and treatment of chronic and acute exposure and inform policy decisions around the uses of OP pesticides in the agricultural industry.

scholarly journals Hollow Fiber Membranes of PCL and PCL/Graphene as Scaffolds with Potential to Develop In Vitro Blood—Brain Barrier Models

Membranes ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 161
Author(s):  
Marián Mantecón-Oria ◽  
Nazely Diban ◽  
Maria T. Berciano ◽  
Maria J. Rivero ◽  
Oana David ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Cell Line ◽  
Blood Brain Barrier ◽  
Hollow Fiber ◽  
Water Flux ◽  
Pharmaceutical Research ◽  
Cell Types ◽  
Brain Barrier ◽  
Blood Brain

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood–brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. A biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, which may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.

scholarly journals Wnt/β-catenin signaling controls development of the blood–brain barrier

2008 ◽  
Vol 183 (3) ◽  
pp. 409-417 ◽  
Author(s):  
Stefan Liebner ◽  
Monica Corada ◽  
Thorsten Bangsow ◽  
Jane Babbage ◽  
Andrea Taddei ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Barrier Properties ◽  
Gene Signature ◽  
Brain Barrier ◽  
Neuronal Function ◽  
Tight Junction Formation ◽  
Blood Brain ◽  
Junction Formation

The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.

scholarly journals Novel Hollow Fiber Membranes of PCL and PCL/Graphene as Scaffolds with Potential to Develop in vitro Blood-brain Barrier Models

2020 ◽  
Author(s):  
Marián Mantecón-Oria ◽  
Nazely Diban ◽  
Maria T. Berciano ◽  
Maria J. Rivero ◽  
Oana David ◽  
...  
Keyword(s):  
Electrical Conductivity ◽  
Cell Line ◽  
Blood Brain Barrier ◽  
Hollow Fiber ◽  
Water Flux ◽  
Pharmaceutical Research ◽  
Cell Types ◽  
Brain Barrier ◽  
Blood Brain

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood-brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. Biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.

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