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Blood–Brain Barrier Breakdown in Stress and Neurodegeneration: Biochemical Mechanisms and New Models for Translational Research

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Abstract

Blood-brain barrier (BBB) is a structural and functional element of the neurovascular unit (NVU), which includes cells of neuronal, glial, and endothelial nature. The main functions of NVU include maintenance of the control of metabolism and chemical homeostasis in the brain tissue, ensuring adequate blood flow in active regions, regulation of neuroplasticity processes, which is realized through intercellular interactions under normal conditions, under stress, in neurodegeneration, neuroinfection, and neurodevelopmental diseases. Current versions of the BBB and NVU models, static and dynamic, have significantly expanded research capabilities, but a number of issues remain unresolved, in particular, personification of the models for a patient. In addition, application of both static and dynamic models has an important problem associated with the difficulty in reproducing pathophysiological mechanisms responsible for the damage of the structural and functional integrity of the barrier in the diseases of the central nervous system. More knowledge on the cellular and molecular mechanisms of BBB and NVU damage in pathology is required to solve this problem. This review discusses current state of the cellular and molecular mechanisms that control BBB permeability, pathobiochemical mechanisms and manifestations of BBB breakdown in stress and neurodegenerative diseases, as well as the problems and prospects of creating in vitro BBB and NVU models for translational studies in neurology and neuropharmacology. Deciphering BBB (patho)physiology will open up new opportunities for further development in the related areas of medicine such as regenerative medicine, neuropharmacology, and neurorehabilitation.

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Abbreviations

Aβ:

amyloid-beta

APP:

amyloid-beta precursor protein

BBB:

blood–brain barrier

CNS:

central nervous system

iPSCs:

induced pluripotent stem cells

NVU:

neurovascular unit

P‑gp:

P-glycoprotein

TEER:

transendothelial electric resistance

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Funding

This work was financially supported by the grant of the President of the Russian Federation for State Support for Leading Scientific Schools of the Russian Federation (# NSH-2547.2020.7).

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  1. Division of Brain Sciences, Research Center of Neurology, 125367, Moscow, Russia

    Alla B. Salmina

  2. Research Institute of Molecular Medicine and Pathobiochemistry, Prof. V. F. Voino-Yasenetsky Krasnoyarsk State Medical University, 660022, Krasnoyarsk, Russia

    Alla B. Salmina, Yuliya K. Komleva, Nataliya A. Malinovskaya, Andrey V. Morgun, Elena A. Teplyashina, Olga L. Lopatina, Yana V. Gorina, Ekaterina V. Kharitonova, Elena D. Khilazheva & Anton N. Shuvaev

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Salmina, A.B., Komleva, Y.K., Malinovskaya, N.A. et al. Blood–Brain Barrier Breakdown in Stress and Neurodegeneration: Biochemical Mechanisms and New Models for Translational Research. Biochemistry Moscow 86, 746–760 (2021). https://doi.org/10.1134/S0006297921060122

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