The Progress in Molecular Transport and Therapeutic Development in Human Blood–Brain Barrier Models in Neurological Disorders

IF 3.6 4区 医学 Q3 CELL BIOLOGY
Joanna Korszun-Karbowniczak, Zuzanna Joanna Krysiak, Joanna Saluk, Marcin Niemcewicz, Robert Zdanowski
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Abstract

The blood–brain barrier (BBB) is responsible for maintaining homeostasis within the central nervous system (CNS). Depending on its permeability, certain substances can penetrate the brain, while others are restricted in their passage. Therefore, the knowledge about BBB structure and function is essential for understanding physiological and pathological brain processes. Consequently, the functional models can serve as a key to help reveal this unknown. There are many in vitro models available to study molecular mechanisms that occur in the barrier. Brain endothelial cells grown in culture are commonly used to modeling the BBB. Current BBB platforms include: monolayer platforms, transwell, matrigel, spheroidal, and tissue-on-chip models. In this paper, the BBB structure, molecular characteristic, as well as its dysfunctions as a consequence of aging, neurodegeneration, or under hypoxia and neurotoxic conditions are presented. Furthermore, the current modelling strategies that can be used to study BBB for the purpose of further drugs development that may reach CNS are also described.

Abstract Image

人类血脑屏障模型在神经系统疾病分子转运和治疗开发方面的进展
血脑屏障(BBB)负责维持中枢神经系统(CNS)内的平衡。根据其渗透性的不同,某些物质可以穿透大脑,而另一些物质则在通过时受到限制。因此,了解 BBB 的结构和功能对于理解大脑的生理和病理过程至关重要。因此,功能模型可以作为帮助揭示这一未知的关键。有许多体外模型可用于研究发生在屏障中的分子机制。培养的脑内皮细胞通常用于建立 BBB 模型。目前的 BBB 平台包括:单层平台、transwell、matrigel、球形和组织芯片模型。本文将介绍 BBB 的结构、分子特征以及衰老、神经变性或缺氧和神经毒性条件下 BBB 的功能障碍。此外,本文还介绍了目前可用于研究 BBB 的建模策略,以便进一步开发可进入中枢神经系统的药物。
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来源期刊
CiteScore
7.70
自引率
0.00%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Cellular and Molecular Neurobiology publishes original research concerned with the analysis of neuronal and brain function at the cellular and subcellular levels. The journal offers timely, peer-reviewed articles that describe anatomic, genetic, physiologic, pharmacologic, and biochemical approaches to the study of neuronal function and the analysis of elementary mechanisms. Studies are presented on isolated mammalian tissues and intact animals, with investigations aimed at the molecular mechanisms or neuronal responses at the level of single cells. Cellular and Molecular Neurobiology also presents studies of the effects of neurons on other organ systems, such as analysis of the electrical or biochemical response to neurotransmitters or neurohormones on smooth muscle or gland cells.
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