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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

(A) Schematic illustration of a resected brain capillary defined by a layer of endothelial cells immersed in a bath. km is the rate constant for passive diffusion across a cell membrane. It is implicitly assumed that passive diffusion across the apical and luminal membranes is the same. kpgp is the rate constant for active transport via efflux pumps from the cell to the lumen. It is assumed that active transport at the apical membrane is negligible. kin and kout represent the overall rate constants for transport from bath to lumen and lumen to bath, respectively. (B) Accumulation of solute in the lumen for a resected capillary with diameter d = 5 μm, P3D = 3 × 10−7 cm s−1, kpgp/km = 0, 5, 10, 20.
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Figure 7: (A) Schematic illustration of a resected brain capillary defined by a layer of endothelial cells immersed in a bath. km is the rate constant for passive diffusion across a cell membrane. It is implicitly assumed that passive diffusion across the apical and luminal membranes is the same. kpgp is the rate constant for active transport via efflux pumps from the cell to the lumen. It is assumed that active transport at the apical membrane is negligible. kin and kout represent the overall rate constants for transport from bath to lumen and lumen to bath, respectively. (B) Accumulation of solute in the lumen for a resected capillary with diameter d = 5 μm, P3D = 3 × 10−7 cm s−1, kpgp/km = 0, 5, 10, 20.

Mentions: Transport across the endothelium of a resected vessel can be analyzed using the model in Figure 7A (Ye and Searson, unpublished). Assuming that intracellular transport is fast in comparison to passive transport across the membrane that the forward and backward rate constants for passive diffusion are the same (km = k−m), and that the solute concentration inside the cell is approximately constant, we obtain (see Supplementary Information):(9)clum(t)=cbath(1+kpgpkm)(1−exp(−tτ))where the time constant τ is given by:(10)τ=r2km(2+kpgpkm)


The blood-brain barrier: an engineering perspective.

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

(A) Schematic illustration of a resected brain capillary defined by a layer of endothelial cells immersed in a bath. km is the rate constant for passive diffusion across a cell membrane. It is implicitly assumed that passive diffusion across the apical and luminal membranes is the same. kpgp is the rate constant for active transport via efflux pumps from the cell to the lumen. It is assumed that active transport at the apical membrane is negligible. kin and kout represent the overall rate constants for transport from bath to lumen and lumen to bath, respectively. (B) Accumulation of solute in the lumen for a resected capillary with diameter d = 5 μm, P3D = 3 × 10−7 cm s−1, kpgp/km = 0, 5, 10, 20.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: (A) Schematic illustration of a resected brain capillary defined by a layer of endothelial cells immersed in a bath. km is the rate constant for passive diffusion across a cell membrane. It is implicitly assumed that passive diffusion across the apical and luminal membranes is the same. kpgp is the rate constant for active transport via efflux pumps from the cell to the lumen. It is assumed that active transport at the apical membrane is negligible. kin and kout represent the overall rate constants for transport from bath to lumen and lumen to bath, respectively. (B) Accumulation of solute in the lumen for a resected capillary with diameter d = 5 μm, P3D = 3 × 10−7 cm s−1, kpgp/km = 0, 5, 10, 20.
Mentions: Transport across the endothelium of a resected vessel can be analyzed using the model in Figure 7A (Ye and Searson, unpublished). Assuming that intracellular transport is fast in comparison to passive transport across the membrane that the forward and backward rate constants for passive diffusion are the same (km = k−m), and that the solute concentration inside the cell is approximately constant, we obtain (see Supplementary Information):(9)clum(t)=cbath(1+kpgpkm)(1−exp(−tτ))where the time constant τ is given by:(10)τ=r2km(2+kpgpkm)

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