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The blood-brain barrier: an engineering perspective.

Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC - Front Neuroeng (2013)

Bottom Line: It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain.Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain.Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, Johns Hopkins University Baltimore, MD, USA ; Institute for Nanobiotechnology, Johns Hopkins University Baltimore, MD, USA.

ABSTRACT
It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.

No MeSH data available.


Related in: MedlinePlus

Schematic illustration of (a) in vitro and (b) in vivo transport measurements. (A) In the 2D transwell assay, a monolayer of cells is formed on a porous membrane separating two compartments. Astrocytes and/or pericytes may be seed on the opposite side of the membrane or in the output chamber. (B)In vivo studies, a solute is injected into the blood of an animal model, and the penetration into the brain measured using a suitable chemical detection assay or imaging technique.
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Figure 4: Schematic illustration of (a) in vitro and (b) in vivo transport measurements. (A) In the 2D transwell assay, a monolayer of cells is formed on a porous membrane separating two compartments. Astrocytes and/or pericytes may be seed on the opposite side of the membrane or in the output chamber. (B)In vivo studies, a solute is injected into the blood of an animal model, and the penetration into the brain measured using a suitable chemical detection assay or imaging technique.

Mentions: The development of an in vitro platform to study transport across the blood-brain barrier has proven challenging. This is not surprising, as brain capillary endothelial cells transduce signals from surrounding astrocytes, pericytes, and from the vascular system. In vitro transport measurements are usually performed using a transwell assay where a confluent monolayer of endothelial cells is formed on a porous support separating two chambers (Figure 4). The permeability can be determined from the transport of a drug or fluorescent probe from the donor side to the acceptor side. Alternatively, ion transport can be characterized in terms of the electrical impedance of the monolayer.


The blood-brain barrier: an engineering perspective.

Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC - Front Neuroeng (2013)

Schematic illustration of (a) in vitro and (b) in vivo transport measurements. (A) In the 2D transwell assay, a monolayer of cells is formed on a porous membrane separating two compartments. Astrocytes and/or pericytes may be seed on the opposite side of the membrane or in the output chamber. (B)In vivo studies, a solute is injected into the blood of an animal model, and the penetration into the brain measured using a suitable chemical detection assay or imaging technique.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757302&req=5

Figure 4: Schematic illustration of (a) in vitro and (b) in vivo transport measurements. (A) In the 2D transwell assay, a monolayer of cells is formed on a porous membrane separating two compartments. Astrocytes and/or pericytes may be seed on the opposite side of the membrane or in the output chamber. (B)In vivo studies, a solute is injected into the blood of an animal model, and the penetration into the brain measured using a suitable chemical detection assay or imaging technique.
Mentions: The development of an in vitro platform to study transport across the blood-brain barrier has proven challenging. This is not surprising, as brain capillary endothelial cells transduce signals from surrounding astrocytes, pericytes, and from the vascular system. In vitro transport measurements are usually performed using a transwell assay where a confluent monolayer of endothelial cells is formed on a porous support separating two chambers (Figure 4). The permeability can be determined from the transport of a drug or fluorescent probe from the donor side to the acceptor side. Alternatively, ion transport can be characterized in terms of the electrical impedance of the monolayer.

Bottom Line: It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain.Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain.Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective.

View Article: PubMed Central - PubMed

Affiliation: Department of Materials Science and Engineering, Johns Hopkins University Baltimore, MD, USA ; Institute for Nanobiotechnology, Johns Hopkins University Baltimore, MD, USA.

ABSTRACT
It has been more than 100 years since Paul Ehrlich reported that various water-soluble dyes injected into the circulation did not enter the brain. Since Ehrlich's first experiments, only a small number of molecules, such as alcohol and caffeine have been found to cross the blood-brain barrier, and this selective permeability remains the major roadblock to treatment of many central nervous system diseases. At the same time, many central nervous system diseases are associated with disruption of the blood-brain barrier that can lead to changes in permeability, modulation of immune cell transport, and trafficking of pathogens into the brain. Therefore, advances in our understanding of the structure and function of the blood-brain barrier are key to developing effective treatments for a wide range of central nervous system diseases. Over the past 10 years it has become recognized that the blood-brain barrier is a complex, dynamic system that involves biomechanical and biochemical signaling between the vascular system and the brain. Here we reconstruct the structure, function, and transport properties of the blood-brain barrier from an engineering perspective. New insight into the physics of the blood-brain barrier could ultimately lead to clinical advances in the treatment of central nervous system diseases.

No MeSH data available.


Related in: MedlinePlus