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

• Published in: Biochemistry (Moscow) Vol. 86; no. 6; pp. 746 - 760
• Main Authors: Salmina, Alla B., Komleva, Yuliya K., Malinovskaya, Nataliya A., Morgun, Andrey V., Teplyashina, Elena A., Lopatina, Olga L., Gorina, Yana V., Kharitonova, Ekaterina V., Khilazheva, Elena D., Shuvaev, Anton N.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01-06-2021; Springer; Springer Nature B.V
• Subjects: Analysis; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Blood flow; Blood-brain barrier; Brain; Brain research; Breakdown; Central nervous system; Cerebral blood flow; Damage; Dynamic models; Endothelium; Gadobutrol; Homeostasis; Life Sciences; Membrane permeability; Microbiology; Molecular modelling; Nervous system diseases; Neural plasticity; Neurodegeneration; Neurodegenerative diseases; Neurodevelopmental disorders; Neurology; Neuronal-glial interactions; Permeability; Regenerative medicine; Rehabilitation; Review; Structure-function relationships; Tissue engineering; Translation; neurodegeneration; stress; blood–brain barrier; brain
• ISSN: 0006-2979; 1608-3040
• DOI: 10.1134/S0006297921060122

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.