scholarly journals Building a better blood-brain barrier

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Courtney Lane-Donovan ◽  
Joachim Herz

A new three-dimensional model of the blood-brain barrier can be used to study processes that are involved in neurodegenerative diseases.

2020 ◽  
Vol 16 (1) ◽  
pp. 015006 ◽  
Author(s):  
Figarol Agathe ◽  
Naka Yasuhiro ◽  
Shigemoto-Mogami Yukari ◽  
Furihata Tomomi ◽  
Sato Kaoru ◽  
...  

F1000Research ◽  
2016 ◽  
Vol 4 ◽  
pp. 1279 ◽  
Author(s):  
Peddagangannagari Sreekanthreddy ◽  
Radka Gromnicova ◽  
Heather Davies ◽  
James Phillips ◽  
Ignacio A. Romero ◽  
...  

The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry. A collagenase digestion method could recover the two cell types separately at 92-96% purity.  Astrocytes grown in the gel matrix do not divide and they have reduced expression of aquaporin-4 and the endothelin receptor, type B compared to two-dimensional cultures, but maintain their expression of glial fibrillary acidic protein. The effects of conditioned media from these astrocytes on the barrier phenotype of the endothelium was compared with media from astrocytes grown conventionally on a two-dimensional (2D) substratum. Both induce the expression of tight junction proteins zonula occludens-1 and claudin-5 in hCMEC/D3 cells, but there was no difference between the induced expression levels by the two media. The model has been used to assess the transport of glucose-coated 4nm gold nanoparticles and for leukocyte migration. TEM was used to trace and quantitate the movement of the nanoparticles across the endothelium and into the astrocytes. This blood-brain barrier model is very suitable for assessing delivery of nanoparticles and larger biomolecules to cells of the CNS, following transport across the endothelium.


Organoid ◽  
2021 ◽  
Vol 1 ◽  
pp. e10
Author(s):  
Hong Nam Kim

The blood-brain barrier (BBB) is a transport barrier that suppresses the translocation of potentially harmful substances to the brain tissue. Although the BBB is known to be associated with many kinds of neuropathology, such as neuroinflammation and neurodegenerative diseases, the conventionally used animal and Transwell models cannot provide sufficient information due to genetic and functional heterogeneity in comparison with humans and limited monitoring capabilities. Recently, human cell-based three-dimensional BBB models have been developed, and these models provide in vivo-like BBB structures and functions. In this review, we provide an overview of the recent advances in BBB models with a particular focus on the simulation of BBB-associated brain physiology and neuropathology. To this end, important factors for recapitulating the in vivo characteristics of the BBB are described. Furthermore, approaches to recapitulate the BBB physiology using engineering methods are summarized. The applications of BBB models in the study of neuropathology, such as inflammation and neurodegenerative diseases, are also presented.


F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 1279 ◽  
Author(s):  
Peddagangannagari Sreekanthreddy ◽  
Radka Gromnicova ◽  
Heather Davies ◽  
James Phillips ◽  
Ignacio A. Romero ◽  
...  

The aim of this study was to develop a three-dimensional (3D) model of the human blood-brain barrier in vitro, which mimics the cellular architecture of the CNS and could be used to analyse the delivery of nanoparticles to cells of the CNS. The model includes human astrocytes set in a collagen gel, which is overlaid by a monolayer of human brain endothelium (hCMEC/D3 cell line). The model was characterised by transmission electron microscopy (TEM), immunofluorescence microscopy and flow cytometry. A collagenase digestion method could recover the two cell types separately at 92-96% purity.  Astrocytes grown in the gel matrix do not divide and they have reduced expression of aquaporin-4 and the endothelin receptor, type B compared to two-dimensional cultures, but maintain their expression of glial fibrillary acidic protein. The effects of conditioned media from these astrocytes on the barrier phenotype of the endothelium was compared with media from astrocytes grown conventionally on a two-dimensional (2D) substratum. Both induce the expression of tight junction proteins zonula occludens-1 and claudin-5 in hCMEC/D3 cells, but there was no difference between the induced expression levels by the two media. The model has been used to assess the transport of glucose-coated 4nm gold nanoparticles and for leukocyte migration. TEM was used to trace and quantitate the movement of the nanoparticles across the endothelium and into the astrocytes. This blood-brain barrier model is very suitable for assessing delivery of nanoparticles and larger biomolecules to cells of the CNS, following transport across the endothelium.


Author(s):  
Falaq Naz ◽  
Yasir Hasan Siddique

: Neurodegenerative diseases including Alzheimer’s, Parkinson’s and Huntington disease are have serious concern due to its effect on the quality of life of affected persons. Neurodegenerative diseases have some limitations for both diagnostic as well as at treatment level. Introducing nanotechnology, for the treatment of these diseases may contribute significantly in solving the problem. There are several treatment strategies for the neurodegenerative diseases, but their limitations are the entry into the due to the presence of the blood-brain barrier (BBB). The present review highlights the application of nanotechnology during last 20 years for the treatment of neurodegenerative diseases.


2003 ◽  
Vol 31 (3) ◽  
pp. 273-276 ◽  
Author(s):  
Hanna Tähti ◽  
Heidi Nevala ◽  
Tarja Toimela

The purpose of this paper is to review the current state of development of advanced in vitro blood–brain barrier (BBB) models. The BBB is a special capillary bed that separates the blood from the central nervous system (CNS) parenchyma. Astrocytes maintain the integrity of the BBB, and, without astrocytic contacts, isolated brain capillary endothelial cells in culture lose their barrier characteristics. Therefore, when developing in vitro BBB models, it is important to add astrocytic factors into the culture system. Recently, novel filter techniques and co-culture methods have made it possible to develop models which resemble the in vivo functions of the BBB in an effective way. With a BBB model, kinetic factors can be added into the in vitro batteries used for evaluating the neurotoxic potential of chemicals. The in vitro BBB model also represents a useful tool for the in vitro prediction of the BBB permeability of drugs, and offers the possibility to scan a large number of drugs for their potential to enter the CNS. Cultured monolayers of brain endothelial cell lines or selected epithelial cell lines, combined with astrocyte and neuron cultures, form a novel three-dimensional technique for the screening of neurotoxic compounds.


Biochimie ◽  
2020 ◽  
Vol 170 ◽  
pp. 203-211 ◽  
Author(s):  
Mayssa Hachem ◽  
Mounir Belkouch ◽  
Amanda Lo Van ◽  
Madeleine Picq ◽  
Nathalie Bernoud-Hubac ◽  
...  

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