Structure and function of the blood–brain barrier

doi:10.1016/J.NBD.2009.07.030

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Structure and function of the blood–brain barrier

Journal Article•DOI•

Structure and function of the blood–brain barrier

N. Joan Abbott¹, Adjanie Patabendige¹, Diana E. M. Dolman¹, Siti R. Yusof¹, David J. Begley¹ - Show less +1 more•Institutions (1)

King's College London¹

01 Jan 2010-Neurobiology of Disease (Neurobiol Dis)-Vol. 37, Iss: 1, pp 13-25

TL;DR: The structure and function of the BBB is summarised, the physical barrier formed by the endothelial tight junctions, and the transport barrier resulting from membrane transporters and vesicular mechanisms are described.

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About: This article is published in Neurobiology of Disease.The article was published on 2010-01-01. It has received 3783 citations till now. The article focuses on the topics: Blood–brain barrier.

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Journal Article•DOI•

Principles of Neural Science

[...]

Michael P. Alexander

06 Jun 1986-JAMA

TL;DR: The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or her own research.

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Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

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7,563 citations

Journal Article•DOI•

Physiology of Microglia

[...]

Helmut Kettenmann¹, Uwe-Karsten Hanisch, Mami Noda, Alexei Verkhratsky•Institutions (1)

Max Delbrück Center for Molecular Medicine¹

01 Apr 2011-Physiological Reviews

TL;DR: Current studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains, and microglial cells are considered the most susceptible sensors of brain pathology.

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Abstract: Microglial cells are the resident macrophages in the central nervous system. These cells of mesodermal/mesenchymal origin migrate into all regions of the central nervous system, disseminate through the brain parenchyma, and acquire a specific ramified morphological phenotype termed "resting microglia." Recent studies indicate that even in the normal brain, microglia have highly motile processes by which they scan their territorial domains. By a large number of signaling pathways they can communicate with macroglial cells and neurons and with cells of the immune system. Likewise, microglial cells express receptors classically described for brain-specific communication such as neurotransmitter receptors and those first discovered as immune cell-specific such as for cytokines. Microglial cells are considered the most susceptible sensors of brain pathology. Upon any detection of signs for brain lesions or nervous system dysfunction, microglial cells undergo a complex, multistage activation process that converts them into the "activated microglial cell." This cell form has the capacity to release a large number of substances that can act detrimental or beneficial for the surrounding cells. Activated microglial cells can migrate to the site of injury, proliferate, and phagocytose cells and cellular compartments.

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2,998 citations

Journal Article•DOI•

Vascular Contributions to Cognitive Impairment and Dementia A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

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Philip B. Gorelick, Angelo Scuteri, Sandra E. Black, Charles DeCarli, Steven M. Greenberg, Costantino Iadecola, Lenore J. Launer, Stéphane Laurent, Oscar L. Lopez, David L. Nyenhuis, Ronald C. Petersen, Julie A. Schneider, Christophe Tzourio, Donna K. Arnett, David A. Bennett, Helena C. Chui, Randall T. Higashida, Ruth Lindquist, Peter M. Nilsson, Gustavo C. Román, Frank W. Sellke, Sudha Seshadri - Show less +18 more

01 Sep 2011-Stroke

TL;DR: This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia and provides evidence that subcortical forms of VCI with white matter hyperintensities and small deep infarcts are common and risk markers for VCI are the same as traditional risk factors for stroke.

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Abstract: Background and Purpose—This scientific statement provides an overview of the evidence on vascular contributions to cognitive impairment and dementia. Vascular contributions to cognitive impairment ...

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2,731 citations

Journal Article•DOI•

Pericytes: developmental, physiological, and pathological perspectives, problems, and promises.

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Annika Armulik¹, Guillem Genové¹, Christer Betsholtz¹•Institutions (1)

Karolinska Institutet¹

16 Aug 2011-Developmental Cell

TL;DR: The history of investigations into pericytes, the mural cells of blood microvessels, are reviewed, emerging concepts are indicated, and problems and promise are pointed out.

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2,120 citations

Cites background from "Structure and function of the blood..."

...What is the origin of tumor pericytes? Coinjection of mouse embryonic fibroblasts from XlacZ4 mice with tumor cells into a subcutaneous space resulted in recruitment of LacZ+ cells exclusively to perivascular locations in the tumors, suggesting that pericytes may be recruited from local immature mesenchymal cells (Abramsson et al., 2002)....
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...…include aSMA (Nisancioglu et al., 2010; Ozawa et al., 2005; Sennino et al., 2007), NG2 (Abramsson et al., 2003), PDGFRb (Ozawa et al., 2005), desmin (Sennino et al., 2007), RGS5 (Berger et al., 2005; Nisancioglu et al., 2008), and the XlacZ4 transgenic mouse (Abramsson et al., 2002) (Figure 7)....
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...As it occurs during physiological angiogenesis, pericytes are recruited into tumor blood vessels by PDGF-B/PDGFRb signaling (Abramsson et al., 2002)....
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...…of mouse embryonic fibroblasts from XlacZ4 mice with tumor cells into a subcutaneous space resulted in recruitment of LacZ+ cells exclusively to perivascular locations in the tumors, suggesting that pericytes may be recruited from local immature mesenchymal cells (Abramsson et al., 2002)....
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..., 2008), and the XlacZ4 transgenic mouse (Abramsson et al., 2002) (Figure 7)....
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Journal Article•DOI•

Blood–brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders

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Melanie D. Sweeney¹, Abhay P. Sagare¹, Berislav V. Zlokovic¹•Institutions (1)

University of Southern California¹

29 Jan 2018-Nature Reviews Neurology

TL;DR: This Review discusses neuroimaging studies in the living human brain and post-mortem tissue as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy.

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Abstract: The blood-brain barrier (BBB) is a continuous endothelial membrane within brain microvessels that has sealed cell-to-cell contacts and is sheathed by mural vascular cells and perivascular astrocyte end-feet The BBB protects neurons from factors present in the systemic circulation and maintains the highly regulated CNS internal milieu, which is required for proper synaptic and neuronal functioning BBB disruption allows influx into the brain of neurotoxic blood-derived debris, cells and microbial pathogens and is associated with inflammatory and immune responses, which can initiate multiple pathways of neurodegeneration This Review discusses neuroimaging studies in the living human brain and post-mortem tissue as well as biomarker studies demonstrating BBB breakdown in Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, multiple sclerosis, HIV-1-associated dementia and chronic traumatic encephalopathy The pathogenic mechanisms by which BBB breakdown leads to neuronal injury, synaptic dysfunction, loss of neuronal connectivity and neurodegeneration are described The importance of a healthy BBB for therapeutic drug delivery and the adverse effects of disease-initiated, pathological BBB breakdown in relation to brain delivery of neuropharmaceuticals are briefly discussed Finally, future directions, gaps in the field and opportunities to control the course of neurological diseases by targeting the BBB are presented

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1,507 citations

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References

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Open Access

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Journal Article•DOI•

Principles of Neural Science

[...]

Michael P. Alexander

06 Jun 1986-JAMA

...read moreread less

7,563 citations

Additional excerpts

...1) (Kandel et al., 2000)....
[...]
...A doi:10.1016/j.nbd.2009.07.030 a b s t r a c t a r t i c l e i n f o...
[...]

Journal Article•DOI•

Astrocyte–endothelial interactions at the blood–brain barrier

[...]

N. Joan Abbott¹, Lars Rönnbäck², Elisabeth Hansson²•Institutions (2)

Wolfson Centre for Age-Related Diseases¹, University of Gothenburg²

01 Jan 2006-Nature Reviews Neuroscience

TL;DR: Specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood–brain barrier function are explored to lead to the development of new protective and restorative therapies.

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Abstract: The blood-brain barrier, which is formed by the endothelial cells that line cerebral microvessels, has an important role in maintaining a precisely regulated microenvironment for reliable neuronal signalling. At present, there is great interest in the association of brain microvessels, astrocytes and neurons to form functional 'neurovascular units', and recent studies have highlighted the importance of brain endothelial cells in this modular organization. Here, we explore specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood-brain barrier function. An understanding of how these interactions are disturbed in pathological conditions could lead to the development of new protective and restorative therapies.

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4,578 citations

"Structure and function of the blood..." refers background or methods in this paper

...The barrier function is not fixed, but can bemodulated and regulated, both in physiology and in pathology (Abbott et al., 2006)....
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...Barrier layers at the key interfaces between blood and neural tissue play a major role in this regulation (Abbott et al., 2006)....
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...Pericytes, microglia and nerve terminals are also closely associated with the endothelium, and play supporting roles in barrier induction, maintenance and function (Abbott et al., 2006; Shimizu et al., 2008; Nakagawa et al., 2009)....
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...In summary the CNS barriers together provide the stable fluid microenvironment that is critical for complex neural function, and protect the CNS from chemical insult and damage....
[...]
...…junctions’ (zonulae occludentes) are a key feature of the BBB and significantly reduce permeation of polar solutes through paracellular diffusional pathways between the endothelial cells from the blood plasma to the brain extracellular fluid (Begley and Brightman, 2003; Wolburg et al., 2009)....
[...]

Journal Article•DOI•

The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders

[...]

Berislav V. Zlokovic¹•Institutions (1)

University of Rochester¹

24 Jan 2008-Neuron

TL;DR: These findings support developments of new therapeutic approaches for chronic neurodegenerative disorders directed at the blood-brain barrier and other nonneuronal cells of the neurovascular unit.

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2,797 citations

"Structure and function of the blood..." refers background in this paper

...…hypoxia and ischemia (Kaur and Ling, 2008); edema (Rosenberg and Yang, 2007); Parkinson's disease and Alzheimer's disease (Desai et al., 2007; Zlokovic, 2008); epilepsy (Remy and Beck, 2006); tumours (Bronger et al., 2005); glaucoma (Grieshaber and Flammer, 2007) and lysosomal storage…...
[...]
...There is a growing list of CNS pathologies involving an element of BBB dysfunction, including multiple sclerosis (Correale and Villa, 2007); hypoxia and ischemia (Kaur and Ling, 2008); edema (Rosenberg and Yang, 2007); Parkinson's disease and Alzheimer's disease (Desai et al., 2007; Zlokovic, 2008); epilepsy (Remy and Beck, 2006); tumours (Bronger et al....
[...]

Journal Article•DOI•

Junctions between intimately apposed cell membranes in the vertebrate brain

[...]

Milton W. Brightman¹, Thomas S. Reese¹•Institutions (1)

National Institutes of Health¹

01 Mar 1969-Journal of Cell Biology

TL;DR: Endothelial and epithelial tight junctions occlude the interspaces between blood and parenchyma or cerebral ventricles, thereby constituting a structural basis for the blood-brain and blood-cerebrospinal fluid barriers.

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Abstract: Certain junctions between ependymal cells, between astrocytes, and between some electrically coupled neurons have heretofore been regarded as tight, pentalaminar occlusions of the intercellular cleft. These junctions are now redefined in terms of their configuration after treatment of brain tissue in uranyl acetate before dehydration. Instead of a median dense lamina, they are bisected by a median gap 20–30 A wide which is continuous with the rest of the interspace. The patency of these "gap junctions" is further demonstrated by the penetration of horseradish peroxidase or lanthanum into the median gap, the latter tracer delineating there a polygonal substructure. However, either tracer can circumvent gap junctions because they are plaque-shaped rather than complete, circumferential belts. Tight junctions, which retain a pentalaminar appearance after uranyl acetate block treatment, are restricted primarily to the endothelium of parenchymal capillaries and the epithelium of the choroid plexus. They form rows of extensive, overlapping occlusions of the interspace and are neither circumvented nor penetrated by peroxidase and lanthanum. These junctions are morphologically distinguishable from the "labile" pentalaminar appositions which appear or disappear according to the preparative method and which do not interfere with the intercellular movement of tracers. Therefore, the interspaces of the brain are generally patent, allowing intercellular movement of colloidal materials. Endothelial and epithelial tight junctions occlude the interspaces between blood and parenchyma or cerebral ventricles, thereby constituting a structural basis for the blood-brain and blood-cerebrospinal fluid barriers.

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2,345 citations

"Structure and function of the blood..." refers background in this paper

...…radius 4.6 Å, Bouldin and Krigman, 1975), when introduced into the cerebral capillary lumen, can be shown by electron microscopy to penetrate the intercellular cleft as far as the tight junctional complexes and then its movement is arrested (Brightman and Reese, 1969; Bouldin and Krigman, 1975)....
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...6 Å, Bouldin and Krigman, 1975), when introduced into the cerebral capillary lumen, can be shown by electron microscopy to penetrate the intercellular cleft as far as the tight junctional complexes and then its movement is arrested (Brightman and Reese, 1969; Bouldin and Krigman, 1975)....
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Journal Article•DOI•

The human ATP-binding cassette (ABC) transporter superfamily

[...]

Michael Dean, Yannick Hamon¹, Giovanna Chimini¹•Institutions (1)

French Institute of Health and Medical Research¹

01 Jul 2001-Journal of Lipid Research

TL;DR: The ATP-binding cassette (ABC) transporters are essential for many processes in the cell and mutations in these genes cause or contribute to several human genetic disorders including cystic fibrosis, neurological disease, retinal degeneration, cholesterol and bile transport defects, anemia, and drug response.

...read moreread less

2,159 citations