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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

Kinetics of solute transport across a 2D monolayer. cout/cin is plotted as a function of time t, with A = 1 cm2, and V = 1 cm3 for (■) P2D = 10−5 cm s−1, and (▲) 10−6 cm s−1, and (•) P2D = 10−7 cm s−1, At short times (inset) where P2DAt/V « 1, the slope is P2DA/V and the rate constant can be obtained from kin,2D = P2DA.
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Figure 6: Kinetics of solute transport across a 2D monolayer. cout/cin is plotted as a function of time t, with A = 1 cm2, and V = 1 cm3 for (■) P2D = 10−5 cm s−1, and (▲) 10−6 cm s−1, and (•) P2D = 10−7 cm s−1, At short times (inset) where P2DAt/V « 1, the slope is P2DA/V and the rate constant can be obtained from kin,2D = P2DA.

Mentions: Integrating Fick's first law and recognizing that kin, 2D = P2DA where P2D is the permeability (cm s−1), we obtain:(6)N(t)=Vcin(1−exp(−P2DAVt))(see Figure 6 and Supplementary Information) (Kedem and Katchalsky, 1958; Siflinger-Birnboim et al., 1987; Dawson, 1991; Tran et al., 2004)At short times where P2DAt « V, the exponential term can be linearized and hence:(7)N(t)=P2DAcint


The blood-brain barrier: an engineering perspective.

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

Kinetics of solute transport across a 2D monolayer. cout/cin is plotted as a function of time t, with A = 1 cm2, and V = 1 cm3 for (■) P2D = 10−5 cm s−1, and (▲) 10−6 cm s−1, and (•) P2D = 10−7 cm s−1, At short times (inset) where P2DAt/V « 1, the slope is P2DA/V and the rate constant can be obtained from kin,2D = P2DA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: Kinetics of solute transport across a 2D monolayer. cout/cin is plotted as a function of time t, with A = 1 cm2, and V = 1 cm3 for (■) P2D = 10−5 cm s−1, and (▲) 10−6 cm s−1, and (•) P2D = 10−7 cm s−1, At short times (inset) where P2DAt/V « 1, the slope is P2DA/V and the rate constant can be obtained from kin,2D = P2DA.
Mentions: Integrating Fick's first law and recognizing that kin, 2D = P2DA where P2D is the permeability (cm s−1), we obtain:(6)N(t)=Vcin(1−exp(−P2DAVt))(see Figure 6 and Supplementary Information) (Kedem and Katchalsky, 1958; Siflinger-Birnboim et al., 1987; Dawson, 1991; Tran et al., 2004)At short times where P2DAt « V, the exponential term can be linearized and hence:(7)N(t)=P2DAcint

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