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.

中文翻译：

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压力和神经变性中的血脑屏障破坏：转化研究的生化机制和新模型

摘要

血脑屏障 (BBB) 是神经血管单元 (NVU) 的结构和功能元件，包括神经元、神经胶质和内皮细胞。NVU 的主要功能包括维持脑组织中代谢和化学稳态的控制，确保活动区域有足够的血流量，调节神经可塑性过程，这是通过正常条件下、压力下、神经变性、神经感染下的细胞间相互作用实现的和神经发育疾病。当前版本的 BBB 和 NVU 模型（静态和动态）显着扩展了研究能力，但许多问题仍未解决，特别是患者模型的拟人化。此外，静态和动态模型的应用都存在一个重要问题，即难以再现导致中枢神经系统疾病中屏障结构和功能完整性受损的病理生理机制。解决这个问题需要更多关于病理学中 BBB 和 NVU 损伤的细胞和分子机制的知识。这篇综述讨论了控制 BBB 通透性的细胞和分子机制的现状、病理生化机制和 BBB 在压力和神经退行性疾病中的分解表现，以及创建血脑屏障的问题和前景。解决这个问题需要更多关于病理学中 BBB 和 NVU 损伤的细胞和分子机制的知识。这篇综述讨论了控制 BBB 通透性的细胞和分子机制的现状、病理生化机制和 BBB 在压力和神经退行性疾病中的分解表现，以及创造血脑屏障的问题和前景。解决这个问题需要更多关于病理学中 BBB 和 NVU 损伤的细胞和分子机制的知识。这篇综述讨论了控制 BBB 通透性的细胞和分子机制的现状、病理生化机制和 BBB 在压力和神经退行性疾病中的分解表现，以及创造血脑屏障的问题和前景。用于神经病学和神经药理学转化研究的体外BBB 和 NVU 模型。破译 BBB（病理）生理学将为再生医学、神经药理学和神经康复等相关医学领域的进一步发展开辟新的机遇。