A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity

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Abstract

The blood–brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for the brain’s metabolic activity as well as neuronal function. Thus, the functional and structural integrity of the BBB is pivotal to maintain the homeostasis of the brain microenvironment. The different cells and structures contributing to developing this barrier are summarized along with the different functions that BBB plays at the brain–blood interface. We also explained the role of shear stress in maintaining BBB integrity. Furthermore, we elaborated on the clinical aspects that correlate between BBB disruption and different neurological and pathological conditions. Finally, we discussed several biomarkers that can help to assess the BBB permeability and integrity in-vitro or in-vivo and briefly explain their advantages and disadvantages.

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Astrocytes: biology and pathology

Michael Sofroniew, Harry V. Vinters (2009)

Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Structure and function of the blood-brain barrier.

N. Abbott, Adjanie Patabendige, Diana Dolman … (2010)

Neural signalling within the central nervous system (CNS) requires a highly controlled microenvironment. Cells at three key interfaces form barriers between the blood and the CNS: the blood-brain barrier (BBB), blood-CSF barrier and the arachnoid barrier. The BBB at the level of brain microvessel endothelium is the major site of blood-CNS exchange. 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. The roles of associated cells are outlined, especially the endfeet of astrocytic glial cells, and pericytes and microglia. The embryonic development of the BBB, and changes in pathology are described. The BBB is subject to short and long-term regulation, which may be disturbed in pathology. Any programme for drug discovery or delivery, to target or avoid the CNS, needs to consider the special features of the BBB.

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Astrocyte-endothelial interactions at the blood-brain barrier.

N. Abbott, Lars Rönnbäck, Elisabeth Hansson (2006)

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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Author and article information

Contributors

Luca Cucullo:

ORCID: http://orcid.org/0000-0002-2827-7162

lcucullo@oakland.edu

Journal

Journal ID (nlm-ta): Fluids Barriers CNS

Journal ID (iso-abbrev): Fluids Barriers CNS

Title: Fluids and Barriers of the CNS

Publisher: BioMed Central (London )

ISSN (Electronic): 2045-8118

Publication date (Electronic): 18 November 2020

Publication date PMC-release: 18 November 2020

Publication date Collection: 2020

Volume: 17

Electronic Location Identifier: 69

Affiliations

[1 ]GRID grid.416992.1, ISNI 0000 0001 2179 3554, Department of Pharmaceutical Sciences, Jerry H. Hodge School of Pharmacy, , Texas Tech University Health Sciences Center, ; 1300 S. Coulter Street, Amarillo, TX 79106 USA

[2 ]GRID grid.261277.7, ISNI 0000 0001 2219 916X, Dept. of Foundational Medical Studies, , Oakland University William Beaumont School of Medicine, ; Office 415, Rochester, MI 48309 USA

Author information

Luca Cucullo http://orcid.org/0000-0002-2827-7162

Article

Publisher ID: 230

DOI: 10.1186/s12987-020-00230-3

PMC ID: 7672931

PubMed ID: 33208141

SO-VID: 2971e67e-2a39-4d38-bf13-294762af891c

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 2 September 2020

Date accepted : 7 November 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000026, National Institute on Drug Abuse;

Award ID: 2R01-DA029121-01A1

Award ID: 1R01DA049737-01

Award Recipient : Luca Cucullo

Funded by: FundRef http://dx.doi.org/10.13039/100000065, National Institute of Neurological Disorders and Stroke;

Award ID: 1R01NS117906-01

Award Recipient : Luca Cucullo

Custom metadata

ScienceOpen disciplines: Neurology

Keywords: blood–brain barrier,tight junctions,transcytosis,disruption,permeability,markers,cns,neuroinflammation,degenerative,teer,integrity

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ScienceOpen disciplines: Neurology

Keywords: blood–brain barrier, tight junctions, transcytosis, disruption, permeability, markers, cns, neuroinflammation, degenerative, teer, integrity

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A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity

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Abstract

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Most cited references 275

Astrocytes: biology and pathology

Structure and function of the blood-brain barrier.

Astrocyte-endothelial interactions at the blood-brain barrier.

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