Glial influence on the blood brain barrier.

doi:10.1002/GLIA.22575

Home
/
Papers
/
Glial influence on the blood brain barrier.

Journal Article•DOI•

Glial influence on the blood brain barrier.

Jorge I. Alvarez¹, Takahiro Katayama¹, Alexandre Prat¹•Institutions (1)

Université de Montréal¹

01 Dec 2013-Glia (Wiley-Blackwell)-Vol. 61, Iss: 12, pp 1939-1958

TL;DR: Recent findings related to the involvement of astrocytes and endothelial cells, including radial glial cells, in the induction of barrier properties during embryogenesis and adulthood are described.

read less

Abstract: The Blood Brain Barrier (BBB) is a specialized vascular structure tightly regulating central nervous system (CNS) homeostasis. Endothelial cells are the central component of the BBB and control of their barrier phenotype resides on astrocytes and pericytes. Interactions between these cells and the endothelium promote and maintain many of the physiological and metabolic characteristics that are unique to the BBB. In this review we describe recent findings related to the involvement of astroglial cells, including radial glial cells, in the induction of barrier properties during embryogenesis and adulthood. In addition, we describe changes that occur in astrocytes and endothelial cells during injury and inflammation with a particular emphasis on alterations of the BBB phenotype.

...read moreread less

Citations

PDF

Open Access

More filters

Journal Article•DOI•

The Blood–Brain Barrier

[...]

Richard Daneman¹, Alexandre Prat²•Institutions (2)

University of California, San Diego¹, Université de Montréal²

01 Jan 2015-Cold Spring Harbor Perspectives in Biology

TL;DR: Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

...read moreread less

Abstract: Blood vessels are critical to deliver oxygen and nutrients to all of the tissues and organs throughout the body. The blood vessels that vascularize the central nervous system (CNS) possess unique properties, termed the blood-brain barrier, which allow these vessels to tightly regulate the movement of ions, molecules, and cells between the blood and the brain. This precise control of CNS homeostasis allows for proper neuronal function and also protects the neural tissue from toxins and pathogens, and alterations of these barrier properties are an important component of pathology and progression of different neurological diseases. The physiological barrier is coordinated by a series of physical, transport, and metabolic properties possessed by the endothelial cells (ECs) that form the walls of the blood vessels, and these properties are regulated by interactions with different vascular, immune, and neural cells. Understanding how these different cell populations interact to regulate the barrier properties is essential for understanding how the brain functions during health and disease.

...read moreread less

1,839 citations

Cites background from "Glial influence on the blood brain ..."

...(C) Magnified EM of ECs depicting a relationship among ECs (with tight junctions [TJ]), PCs, basement membranes (BMs), and astrocyte endfeet (AE)....
[...]
...…engineered to lose the signal transducer Smo on ECs had a significant increase in BBB permeability that correlated with a decrease in junctional protein expression and disturbed BMs (Alvarez et al. 2011a, 2013), supporting the concept that the Hh pathway has a significant influence on BBB function....
[...]
...These BMs provide an anchor for many signaling processes at the vasculature, but also provide an additional barrier for molecules and cells to cross before accessing the neural tissue....
[...]
...The vascular tube is surrounded by two BMs, the inner vascular BM and the outer parenchymal BM, also called the vascular glia limitans perivascularis (Del Zoppo et al. 2006; Sorokin 2010)....
[...]
...These BMs are comprised of different secreted molecules including type IV collagens, laminin, nidogen, heparin sulfate proteoglycans, and other glycoproteins....
[...]

Journal Article•DOI•

Astrocyte barriers to neurotoxic inflammation

[...]

Michael V. Sofroniew¹•Institutions (1)

University of California, Los Angeles¹

01 May 2015-Nature Reviews Neuroscience

TL;DR: Evidence that astrocytes have crucial roles in attracting and restricting CNS inflammation, with important implications for diverse CNS disorders is discussed.

...read moreread less

Abstract: Astrocytes form borders (glia limitans) that separate neural from non-neural tissue along perivascular spaces, meninges and tissue lesions in the CNS. Transgenic loss-of-function studies reveal that astrocyte borders and scars serve as functional barriers that restrict the entry of inflammatory cells into CNS parenchyma in health and disease. Astrocytes also have powerful pro-inflammatory potential. Thus, astrocytes are emerging as pivotal regulators of CNS inflammatory responses. This Review discusses evidence that astrocytes have crucial roles in attracting and restricting CNS inflammation, with important implications for diverse CNS disorders.

...read moreread less

823 citations

Journal Article•DOI•

The blood–brain barrier and blood–tumour barrier in brain tumours and metastases

[...]

Costas D. Arvanitis¹, Gino B. Ferraro², Rakesh K. Jain²•Institutions (2)

Georgia Institute of Technology¹, Harvard University²

01 Jan 2020-Nature Reviews Cancer

TL;DR: A deeper understanding of the BBB and BTB through the application of single-cell sequencing and imaging techniques, and the development of biomarkers of BBB integrity along with systems biology approaches, should enable new personalized treatment strategies for primary brain malignancies and brain metastases.

...read moreread less

Abstract: For a blood-borne cancer therapeutic agent to be effective, it must cross the blood vessel wall to reach cancer cells in adequate quantities, and it must overcome the resistance conferred by the local microenvironment around cancer cells. The brain microenvironment can thwart the effectiveness of drugs against primary brain tumours as well as brain metastases. In this Review, we highlight the cellular and molecular components of the blood–brain barrier (BBB), a specialized neurovascular unit evolved to maintain brain homeostasis. Tumours are known to compromise the integrity of the BBB, resulting in a vasculature known as the blood–tumour barrier (BTB), which is highly heterogeneous and characterized by numerous distinct features, including non-uniform permeability and active efflux of molecules. We discuss the challenges posed by the BBB and BTB for drug delivery, how multiple cell types dictate BBB function and the role of the BTB in disease progression and treatment. Finally, we highlight emerging molecular, cellular and physical strategies to improve drug delivery across the BBB and BTB and discuss their impact on improving conventional as well as emerging treatments, such as immune checkpoint inhibitors and engineered T cells. A deeper understanding of the BBB and BTB through the application of single-cell sequencing and imaging techniques, and the development of biomarkers of BBB integrity along with systems biology approaches, should enable new personalized treatment strategies for primary brain malignancies and brain metastases. This Review discusses the structure and function of the blood–brain barrier (BBB) and how brain tumours and brain metastases compromise BBB integrity. It also discusses the challenges the BBB poses for cancer therapy and how these might be overcome.

...read moreread less

752 citations

Journal Article•DOI•

Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits

[...]

Milos Pekny¹, Marcela Pekna²•Institutions (2)

University of Gothenburg¹, Florey Institute of Neuroscience and Mental Health²

01 Oct 2014-Physiological Reviews

TL;DR: Understanding the multifaceted roles of astrocytes in the healthy and diseased CNS will undoubtedly contribute to the development of treatment strategies that will, in a context-dependent manner and at appropriate time points, modulate reactive astrogliosis to promote brain repair and reduce the neurological impairment.

...read moreread less

Abstract: Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions including the generation of new nerve cells and structural as well as functional synapse remodeling Reactive gliosis or reactive astrogliosis is a term coined for the morphological and functional changes seen in astroglial cells/astrocytes responding to CNS injury and other neurological diseases Whereas this defensive reaction of astrocytes is conceivably aimed at handling the acute stress, limiting tissue damage, and restoring homeostasis, it may also inhibit adaptive neural plasticity mechanisms underlying recovery of function Understanding the multifaceted roles of astrocytes in the healthy and diseased CNS will undoubtedly contribute to the development of treatment strategies that will, in a context-dependent manner and at appropriate time points, modulate reactive astrogliosis to promote brain repair and reduce the neurological impairment

...read moreread less

668 citations

Cites background from "Glial influence on the blood brain ..."

...It is possible that all astrocytes participate in the astrovascular interface with at least one astrocyte process being in contact with a blood vessel (244), and through their endfeet regulate the transport of water (89) and other substances between the intravascular space and brain parenchyma (5)....
[...]

Journal Article•DOI•

Overcoming the blood-brain tumor barrier for effective glioblastoma treatment

[...]

O. van Tellingen¹, B. Yetkin-Arik², M.C. de Gooijer¹, Pieter Wesseling², Pieter Wesseling³, Thomas Wurdinger², Thomas Wurdinger⁴, H.E. de Vries² - Show less +4 more•Institutions (4)

Netherlands Cancer Institute¹, VU University Medical Center², Radboud University Nijmegen³, Harvard University⁴

01 Mar 2015-Drug Resistance Updates

TL;DR: Methods to overcome the blood-brain tumor barrier barrier (BBTB) are provided, including osmotic blood- brain barrier disruption (BBBD), bradykinin receptor-mediated BBTB opening, inhibition of multidrug efflux transporters, receptor- mediated transport systems and physiological circumvention of the BBTB.

...read moreread less

655 citations

1
2
3
4
…
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82

Collapse

References

PDF

Open Access

More filters

Journal Article•DOI•

Mechanisms of angiogenesis

[...]

Werner Risau¹•Institutions (1)

Max Planck Society¹

17 Apr 1997-Nature

TL;DR: Understanding of the molecular basis underlying angiogenesis, particularly from the study of mice lacking some of the signalling systems involved, has greatly improved, and may suggest new approaches for treating conditions such as cancer that depend onAngiogenesis.

...read moreread less

Abstract: After the developing embryo has formed a primary vascular plexus by a process termed vasculogenesis, further blood vessels are generated by both sprouting and non-sprouting angiogenesis, which are progressively pruned and remodelled into a functional adult circulatory system. Recent results, particularly from the study of mice lacking some of the signalling systems involved, have greatly improved our understanding of the molecular basis underlying these events, and may suggest new approaches for treating conditions such as cancer that depend on angiogenesis.

...read moreread less

5,793 citations

"Glial influence on the blood brain ..." refers background in this paper

...…of the primitive capillary network located in the perineural vascular plexus expand by angiogenesis into the CNS parenchyma at embryonic day 11 in mouse (Risau, 1997; Risau and Wolburg, 1990) and around the 8th week of gestation in humans (Ballabh et al., 2005; Bar, 1980; Norman and O’Kusky, 1986)....
[...]
...Blood vessel development within the CNS begins when vascular elements of the primitive capillary network located in the perineural vascular plexus expand by angiogenesis into the CNS parenchyma at embryonic day 11 in mouse (Risau, 1997; Risau and Wolburg, 1990) and around the 8th week of gestation in humans (Ballabh et al....
[...]

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.

...read moreread less

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.

...read moreread less

4,578 citations

"Glial influence on the blood brain ..." refers background in this paper

...Control of BBB Phenotype by Astroglial Cues During Homeostasis In addition to the support provided by astrocytes to postnatal BBB development, the persistence of a functional BBB throughout adulthood is maintained and regulated by numerous factors unique to the microniche of the NVU (Abbott et al., 2006; Haseloff et al., 2005)....
[...]
...Astrocyte-BBB-EC interactions are also known to regulate vascular proliferation, angiogenesis, EC morphology, and ultimately influence the phenotype of the barrier under pathological conditions (Abbott et al., 2006; Prat et al., 2001; Wolburg and Lippoldt, 2002; Wosik et al., 2007)....
[...]
...Conversely, when nonCNS ECs are cultured in the presence of astrocytes, or astrocyte-secreted factors, a series of BBB-specific properties, such as P-glycoprotein (p-gp) and TJ expression can be induced (Abbott et al., 2006; Prat et al., 2001; Wosik et al., 2007)....
[...]
...In addition to the support provided by astrocytes to postnatal BBB development, the persistence of a functional BBB throughout adulthood is maintained and regulated by numerous factors unique to the microniche of the NVU (Abbott et al., 2006; Haseloff et al., 2005)....
[...]
...Astrocyte-BBB-EC interactions are also known to regulate vascular proliferation, angiogenesis, EC morphology, and ultimately influence the phenotype of the barrier under pathological conditions (Abbott et al., 2006; Prat et al., 2001; Wolburg and Lippoldt, 2002; Wosik et al., 2007)....
[...]

Journal Article•DOI•

Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice.

[...]

Fouad Shalaby¹, Janet Rossant¹, Janet Rossant², Terry P. Yamaguchi¹, Terry P. Yamaguchi², Marina Gertsenstein¹, Xiang-Fu Wu³, Xiang-Fu Wu², Martin L. Breitman¹, Martin L. Breitman², Andre C. Schuh - Show less +7 more•Institutions (3)

Mount Sinai Hospital, Toronto¹, University of Toronto², Canadian Red Cross³

06 Jul 1995-Nature

TL;DR: The generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells is reported, indicating that FlK-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo.

...read moreread less

Abstract: The receptor tyrosine kinase Flk-1 (ref. 1) is believed to play a pivotal role in endothelial development. Expression of the Flk-1 receptor is restricted to endothelial cells and their embryonic precursors, and is complementary to that of its ligand, vascular endothelial growth factor (VEGF), which is an endothelial-specific mitogen. Highest levels of flk-1 expression are observed during embryonic vasculogenesis and angiogenesis, and during pathological processes associated with neovascularization, such as tumour angiogenesis. Because flk-1 expression can be detected in presumptive mesodermal yolk-sac blood-island progenitors as early as 7.0 days postcoitum, Flk-1 may mark the putative common embryonic endothelial and haematopoietic precursor, the haemangioblast, and thus may also be involved in early haematopoiesis. Here we report the generation of mice deficient in Flk-1 by disruption of the gene using homologous recombination in embryonic stem (ES) cells. Embryos homozygous for this mutation die in utero between 8.5 and 9.5 days post-coitum, as a result of an early defect in the development of haematopoietic and endothelial cells. Yolk-sac blood islands were absent at 7.5 days, organized blood vessels could not be observed in the embryo or yolk sac at any stage, and haematopoietic progenitors were severely reduced. These results indicate that Flk-1 is essential for yolk-sac blood-island formation and vasculogenesis in the mouse embryo.

...read moreread less

4,063 citations

"Glial influence on the blood brain ..." refers background in this paper

...During development, VEGF is required for the formation, remodeling and survival of embryonic blood vessels as embryos lacking VEGF develop few or no angioblasts and die prematurely (Shalaby et al., 1995)....
[...]
...During development, VEGF is required for the formation, remodeling and survival of embryonic blood vessels as embryos lacking VEGF develop few or no angioblasts and die prematurely (Shalaby et al., 1995)....
[...]

Journal Article•DOI•

Apolipoprotein E: cholesterol transport protein with expanding role in cell biology.

[...]

Robert W. Mahley¹•Institutions (1)

University of California, San Francisco¹

29 Apr 1988-Science

TL;DR: Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body.

...read moreread less

Abstract: Apolipoprotein E is a plasma protein that serves as a ligand for low density lipoprotein receptors and, through its interaction with these receptors, participates in the transport of cholesterol and other lipids among various cells of the body A mutant form of apolipoprotein E that is defective in binding to low density lipoprotein receptors is associated with familial type III hyperlipoproteinemia, a genetic disorder characterized by elevated plasma cholesterol levels and accelerated coronary artery disease Apolipoprotein E is synthesized in various organs, including liver, brain, spleen, and kidney, and is present in high concentrations in interstitial fluid, where it appears to participate in cholesterol redistribution from cells with excess cholesterol to those requiring cholesterol Apolipo-protein E also appears to be involved in the repair response to tissue injury; for example, markedly increased amounts of apolipoprotein E are found at sites of peripheral nerve injury and regeneration Other functions of apolipoprotein E, unrelated to lipid transport, are becoming known, including immunoregulation and modulation of cell growth and differentiation

...read moreread less

3,967 citations

Journal Article•DOI•

An Energy Budget for Signaling in the Grey Matter of the Brain

[...]

David Attwell¹, Simon B. Laughlin²•Institutions (2)

University College London¹, University of Cambridge²

01 Oct 2001-Journal of Cerebral Blood Flow and Metabolism

TL;DR: The estimates of energy usage predict the use of distributed codes, with ≤15% of neurons simultaneously active, to reduce energy consumption and allow greater computing power from a fixed number of neurons.

...read moreread less

Abstract: Anatomic and physiologic data are used to analyze the energy expenditure on different components of excitatory signaling in the grey matter of rodent brain. Action potentials and postsynaptic effects of glutamate are predicted to consume much of the energy (47% and 34%, respectively), with the resting potential consuming a smaller amount (13%), and glutamate recycling using only 3%. Energy usage depends strongly on action potential rate--an increase in activity of 1 action potential/cortical neuron/s will raise oxygen consumption by 145 mL/100 g grey matter/h. The energy expended on signaling is a large fraction of the total energy used by the brain; this favors the use of energy efficient neural codes and wiring patterns. Our estimates of energy usage predict the use of distributed codes, with

...read moreread less

2,912 citations