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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Gold, Paul / Holsboer, Florian / Korth, Carsten / Li, Jay-Shake / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

IMPACT FACTOR 2018: 2.157
5-year IMPACT FACTOR: 2.935

CiteScore 2017: 2.81

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Volume 29, Issue 5


Gliotransmitters and cytokines in the control of blood-brain barrier permeability

Elena D. Osipova
  • Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
  • Interdisciplinary Center of Critical Technologies in Medicine, Department of Physiology of Humans and Animals, Saratov State University named after N.G. Chernyshevsky, Saratov 410012, Russia
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/ Oxana V. Semyachkina-Glushkovskaya
  • Interdisciplinary Center of Critical Technologies in Medicine, Department of Physiology of Humans and Animals, Saratov State University named after N.G. Chernyshevsky, Saratov 410012, Russia
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/ Andrey V. Morgun
  • Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
  • Interdisciplinary Center of Critical Technologies in Medicine, Department of Physiology of Humans and Animals, Saratov State University named after N.G. Chernyshevsky, Saratov 410012, Russia
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/ Natalia V. Pisareva
  • Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
  • Department of Biochemistry, Medical, Pharmaceutical and Toxicological Chemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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/ Natalia A. Malinovskaya
  • Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
  • Department of Biochemistry, Medical, Pharmaceutical and Toxicological Chemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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/ Elizaveta B. Boitsova
  • Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
  • Department of Biochemistry, Medical, Pharmaceutical and Toxicological Chemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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/ Elena A. Pozhilenkova
  • Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
  • Department of Biochemistry, Medical, Pharmaceutical and Toxicological Chemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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/ Olga A. Belova
  • Department of Traumatology, Orthopedics and Neurosurgery, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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/ Vladimir V. Salmin
  • Interdisciplinary Center of Critical Technologies in Medicine, Department of Physiology of Humans and Animals, Saratov State University named after N.G. Chernyshevsky, Saratov 410012, Russia
  • Department of Medical and Biological Physics, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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/ Tatiana E. Taranushenko
  • Department of Pediatrics, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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/ Mami Noda
  • Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 8128582, Japan
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/ Alla B. Salmina
  • Corresponding author
  • Research Institute of Molecular Medicine and Pathobiochemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, P. Zheleznyaka str., 1, Krasnoyarsk 660022, Russia
  • Interdisciplinary Center of Critical Technologies in Medicine, Department of Physiology of Humans and Animals, Saratov State University named after N.G. Chernyshevsky, Saratov 410012, Russia
  • Department of Biochemistry, Medical, Pharmaceutical and Toxicological Chemistry, Krasnoyarsk State Medical University named after Prof. V.F. Voino-Yasenetsky, Krasnoyarsk 660022, Russia
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Published Online: 2018-01-08 | DOI: https://doi.org/10.1515/revneuro-2017-0092


The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions. The release of gliotransmitters or cytokines by activated astroglial and microglial cells is provided by distinct mechanisms, affects intercellular communication, and results in the establishment of microenvironment controlling BBB permeability and neuroinflammation. Glial glutamate transporters and connexin and pannexin hemichannels working in the tight functional coupling with the purinergic system serve as promising molecular targets for manipulating the intercellular communications that control BBB permeability in brain pathologies associated with excessive angiogenesis, cerebrovascular remodeling, and BBB-mediated neuroinflammation. Substantial progress in deciphering the molecular mechanisms underlying the (patho)physiology of perivascular glia provides promising approaches to novel clinically relevant therapies for brain disorders. The present review summarizes the current understandings on the secretory machinery expressed in glial cells (glutamate transporters, connexin and pannexin hemichannels, exocytosis mechanisms, membrane-derived microvesicles, and inflammasomes) and the role of secreted gliotransmitters and cytokines in the regulation of NVU and BBB permeability in (patho)physiologic conditions.

Keywords: astrocyte; ATP; blood-brain barrier; cytokines; endothelium; glutamate; microglia; pericyte


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About the article

Received: 2017-11-02

Accepted: 2017-11-26

Published Online: 2018-01-08

Published in Print: 2018-07-26

Citation Information: Reviews in the Neurosciences, Volume 29, Issue 5, Pages 567–591, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: https://doi.org/10.1515/revneuro-2017-0092.

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