Barriers are the hallmark of a healthy physiology, blood-brain barrier (BBB) being a tough nut to crack for most of the antigens and chemical substances. The presence of tight junctions plays a remarkable role in defending the brain from antigenic and pathogenic attacks. BBB constitutes a diverse assemblage of multiple physical and chemical barriers that judiciously restrict the flux of blood solutes into and out of the brain. Restrictions through the paracellular pathway and the tight junctions between intercellular clefts, together create well regulated metabolic and transport barricades, critical to brain pathophysiology. The brain being impermeable to many essential metabolites and nutrients regulates transportation via specialized transport systems across the endothelial abluminal and luminal membranes. The epithelial cells enveloping capillaries of the choroid plexus regulates the transport of complement, growth factors, hormones, microelements, peptides and trace elements into ventricles. Nerve terminals, microglia, and pericytes associated with the endothelium support barrier induction and function, ensuring an optimally stable ionic microenvironment that facilitates neurotransmission, orchestrated by multiple ion channels (Na+, K+ Mg2+, Ca2+) and transporters. Brain pathology which can develop due to genetic mutations or secondary to other cerebrovascular, neurodegenerative diseases can cause aberration in the microvasculature of CNS which is the uniqueness of BBB. This can also alter BBB permeation and result in BBB breakdown and other neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. The concluding section outlines contemporary trends in drug discovery, focusing on molecular determinants of BBB permeation and novel drug-delivery systems, such as dendrimers, liposomes, nanoparticles, nanogels, etc.

中文翻译：

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重新审视血脑屏障：药物分子运输中的一个难题。

屏障是健康生理的标志，血脑屏障 (BBB) 是大多数抗原和化学物质难以破解的难题。紧密连接的存在在保护大脑免受抗原性和致病性攻击方面起着显着的作用。BBB 构成了多种物理和化学屏障的多样化组合，可明智地限制血液溶质进出大脑的流量。通过细胞旁通路的限制和细胞间裂隙之间的紧密连接共同形成了良好调节的代谢和运输障碍，这对脑病理生理学至关重要。大脑对许多必需的代谢物和营养物质是不可渗透的，它通过跨内皮外腔和腔内膜的专门运输系统来调节运输。包裹脉络丛毛细血管的上皮细胞调节补体、生长因子、激素、微量元素、肽和微量元素向心室的转运。与内皮相关的神经末梢、小胶质细胞和周细胞支持屏障诱导和功能，确保最佳稳定的离子微环境有利于神经传递，由多个离子通道（Na+、K+、Mg2+、Ca2+）和转运蛋白协调。由于基因突变或继发于其他脑血管、神经退行性疾病而导致的脑病理学可导致中枢神经系统微血管系统异常，这是 BBB 的独特之处。这也会改变 BBB 的渗透，导致 BBB 分解和其他神经退行性疾病，如阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和多发性硬化症。结论部分概述了药物发现的当代趋势，重点关注 BBB 渗透的分子决定因素和新型药物输送系统，如树枝状聚合物、脂质体、纳米颗粒、纳米凝胶等。