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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

The blood-brain barrier. (A) Schematic illustration of transport across the brain microvascular endothelial cells (BMECs) that form the lumen of brain capillaries. Paracellular transport is severely restricted due to the formation of tight junctions between endothelial cells. Metabolic nutrients and other essential molecules are transported across the luminal and abluminal membranes by channels, pumps, or mediated transport systems. Small lipophilic molecules can passively diffuse across the lipid bilayer but, in many cases, are returned to the blood by efflux pumps. (B) Proposed molecular interactions at tight junctions. Lateral association of claudins (cis-interaction) results in the formation of oligomers whereas association of claudins on opposing membranes (trans-interaction) results in tight junction formation. Multiple regions of trans-interactions appear as particles in electron microscopy images.
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Figure 1: The blood-brain barrier. (A) Schematic illustration of transport across the brain microvascular endothelial cells (BMECs) that form the lumen of brain capillaries. Paracellular transport is severely restricted due to the formation of tight junctions between endothelial cells. Metabolic nutrients and other essential molecules are transported across the luminal and abluminal membranes by channels, pumps, or mediated transport systems. Small lipophilic molecules can passively diffuse across the lipid bilayer but, in many cases, are returned to the blood by efflux pumps. (B) Proposed molecular interactions at tight junctions. Lateral association of claudins (cis-interaction) results in the formation of oligomers whereas association of claudins on opposing membranes (trans-interaction) results in tight junction formation. Multiple regions of trans-interactions appear as particles in electron microscopy images.

Mentions: The tight junctions formed by brain microvascular endothelial cells (BMECs) regulate paracellular transport whereas transcellular transport is regulated by specialized transporters, pumps, and receptors (Figure 1) (Chishty et al., 2001; Demeule et al., 2002; Hawkins et al., 2002; Ohtsuki and Terasaki, 2007; Ueno, 2009; Abbott et al., 2010; Hartz and Bauer, 2011).


The blood-brain barrier: an engineering perspective.

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

The blood-brain barrier. (A) Schematic illustration of transport across the brain microvascular endothelial cells (BMECs) that form the lumen of brain capillaries. Paracellular transport is severely restricted due to the formation of tight junctions between endothelial cells. Metabolic nutrients and other essential molecules are transported across the luminal and abluminal membranes by channels, pumps, or mediated transport systems. Small lipophilic molecules can passively diffuse across the lipid bilayer but, in many cases, are returned to the blood by efflux pumps. (B) Proposed molecular interactions at tight junctions. Lateral association of claudins (cis-interaction) results in the formation of oligomers whereas association of claudins on opposing membranes (trans-interaction) results in tight junction formation. Multiple regions of trans-interactions appear as particles in electron microscopy images.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: The blood-brain barrier. (A) Schematic illustration of transport across the brain microvascular endothelial cells (BMECs) that form the lumen of brain capillaries. Paracellular transport is severely restricted due to the formation of tight junctions between endothelial cells. Metabolic nutrients and other essential molecules are transported across the luminal and abluminal membranes by channels, pumps, or mediated transport systems. Small lipophilic molecules can passively diffuse across the lipid bilayer but, in many cases, are returned to the blood by efflux pumps. (B) Proposed molecular interactions at tight junctions. Lateral association of claudins (cis-interaction) results in the formation of oligomers whereas association of claudins on opposing membranes (trans-interaction) results in tight junction formation. Multiple regions of trans-interactions appear as particles in electron microscopy images.
Mentions: The tight junctions formed by brain microvascular endothelial cells (BMECs) regulate paracellular transport whereas transcellular transport is regulated by specialized transporters, pumps, and receptors (Figure 1) (Chishty et al., 2001; Demeule et al., 2002; Hawkins et al., 2002; Ohtsuki and Terasaki, 2007; Ueno, 2009; Abbott et al., 2010; Hartz and Bauer, 2011).

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