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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 neurovascular unit. The microvascular endothelial cells that form the lumen of brain capillaries are partially covered by pericytes and basement membrane, and almost completely surrounded by the end feet of astrocytes. Functional interactions between BMECs, astrocytes, pericytes, other glial cells, and neurons are key to regulating brain homeostasis. Blood flow is associated both biomechanical and biochemical signaling mediated by multiple cell types and soluble factors. The brain microvascular endothelial cells function in a cylindrical geometry with high curvature and experience shear stress resulting from blood flow. The BMECs and pericytes are surrounded by basement membrane consisting primarily of fibronectin, laminin 1, and collagen type IV. The extra-cellular matrix in the brain is based on hyaluronic acid.
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Figure 2: The neurovascular unit. The microvascular endothelial cells that form the lumen of brain capillaries are partially covered by pericytes and basement membrane, and almost completely surrounded by the end feet of astrocytes. Functional interactions between BMECs, astrocytes, pericytes, other glial cells, and neurons are key to regulating brain homeostasis. Blood flow is associated both biomechanical and biochemical signaling mediated by multiple cell types and soluble factors. The brain microvascular endothelial cells function in a cylindrical geometry with high curvature and experience shear stress resulting from blood flow. The BMECs and pericytes are surrounded by basement membrane consisting primarily of fibronectin, laminin 1, and collagen type IV. The extra-cellular matrix in the brain is based on hyaluronic acid.

Mentions: Historically, the blood-brain barrier has been defined by the layer of endothelial cells that form the vessel/capillary walls. More recently, the concept of the neurovascular unit has been introduced to recognize that brain health depends on functional interactions between neurons and non-neuronal cells such as vascular cells (endothelial cells and pericytes) and glia (astrocytes, microglia, and oligodendroglia; Figure 2) (Hawkins and Davis, 2005; Abbott et al., 2010). This is a highly dynamic system in which cells transduce biochemical and biomechanical signals in complex microenvironments involving basement membrane and extracellular matrix. These non-neuronal cells are responsible for the physical, biochemical, and immune barriers of the CNS that regulate the microenvironment of the neurons which is key for signal transduction, remodeling, angiogenesis, and neurogenesis.


The blood-brain barrier: an engineering perspective.

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

The neurovascular unit. The microvascular endothelial cells that form the lumen of brain capillaries are partially covered by pericytes and basement membrane, and almost completely surrounded by the end feet of astrocytes. Functional interactions between BMECs, astrocytes, pericytes, other glial cells, and neurons are key to regulating brain homeostasis. Blood flow is associated both biomechanical and biochemical signaling mediated by multiple cell types and soluble factors. The brain microvascular endothelial cells function in a cylindrical geometry with high curvature and experience shear stress resulting from blood flow. The BMECs and pericytes are surrounded by basement membrane consisting primarily of fibronectin, laminin 1, and collagen type IV. The extra-cellular matrix in the brain is based on hyaluronic acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: The neurovascular unit. The microvascular endothelial cells that form the lumen of brain capillaries are partially covered by pericytes and basement membrane, and almost completely surrounded by the end feet of astrocytes. Functional interactions between BMECs, astrocytes, pericytes, other glial cells, and neurons are key to regulating brain homeostasis. Blood flow is associated both biomechanical and biochemical signaling mediated by multiple cell types and soluble factors. The brain microvascular endothelial cells function in a cylindrical geometry with high curvature and experience shear stress resulting from blood flow. The BMECs and pericytes are surrounded by basement membrane consisting primarily of fibronectin, laminin 1, and collagen type IV. The extra-cellular matrix in the brain is based on hyaluronic acid.
Mentions: Historically, the blood-brain barrier has been defined by the layer of endothelial cells that form the vessel/capillary walls. More recently, the concept of the neurovascular unit has been introduced to recognize that brain health depends on functional interactions between neurons and non-neuronal cells such as vascular cells (endothelial cells and pericytes) and glia (astrocytes, microglia, and oligodendroglia; Figure 2) (Hawkins and Davis, 2005; Abbott et al., 2010). This is a highly dynamic system in which cells transduce biochemical and biomechanical signals in complex microenvironments involving basement membrane and extracellular matrix. These non-neuronal cells are responsible for the physical, biochemical, and immune barriers of the CNS that regulate the microenvironment of the neurons which is key for signal transduction, remodeling, angiogenesis, and neurogenesis.

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