A highly regulated endoneurial microenvironment is required for normal axonal function in peripheral nerves and nerve roots, which structurally consist of an outer collagenous epineurium, inner perineurium consisting of multiple concentric layers of specialized epithelioid myofibroblasts that surround the innermost endoneurium, which consists of myelinated and unmyelinated axons embedded in a looser mesh of collagen fibers. Endoneurial homeostasis is achieved by tight junction-forming endoneurial microvessels that control ion, solute, water, nutrient, macromolecule and leukocyte influx and efflux between the bloodstream and endoneurium, and the innermost layers of the perineurium that control interstitial fluid component flux between the freely permeable epineurium and endoneurium. Strictly speaking, endoneurial microvascular endothelium should be considered the blood-nerve barrier (BNB) due to direct communication with circulating blood. The mammalian BNB is considered the second most restrictive vascular system after the blood-brain barrier (BBB) based on classic in situ permeability studies. Structural alterations in endoneurial microvessels or interactions with hematogenous leukocytes have been described in several human peripheral neuropathies; however major advances in BNB biology in health and disease have been limited over the past 50 years. Guided by transcriptome and proteome studies of normal and pathologic human peripheral nerves, purified primary and immortalized human endoneurial endothelial cells that form the BNB and leukocytes from patients with well-characterized peripheral neuropathies, validated by in situ or ex vivo protein expression studies, data are emerging on the molecular and functional characteristics of the human BNB in health and in specific peripheral neuropathies, as well as chronic neuropathic pain. These early advancements have the potential to not only increase our understanding of how the BNB works and adapts or fails to adapt to varying insult, but provide insights relevant to pathogenic leukocyte trafficking, with translational potential and specific therapeutic application for chronic peripheral neuropathies and neuropathic pain.

中文翻译：

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人类血液神经屏障在健康和疾病中的生物学。

外周神经和神经根的正常轴突功能需要高度调节的神经内膜微环境，其结构由外部胶原神经外膜，内部神经周膜组成，该神经周神经膜由多个同心的特殊上皮样成肌纤维细胞层组成，围绕着最里面的神经内膜，由髓鞘和非髓鞘组成轴突嵌在较疏松的胶原纤维网中。通过紧密连接形成的神经内膜微血管可实现神经内膜稳态，该微血管控制离子，溶质，水，营养物，大分子和白细胞在血流和神经内膜之间的流入和流出，以及在神经内膜的最内层控制自由渗透性之间的组织液成分通量神经外膜和神经内膜。严格来说，由于与循环血液直接连通，因此应将神经内膜微血管内皮视为血神经屏障（BNB）。根据经典的原位通透性研究，哺乳动物BNB被认为是仅次于血脑屏障（BBB）的第二大限制性血管系统。在几种人类周围神经病中，已经描述了神经内膜微血管的结构改变或与血白细胞的相互作用。然而，在过去的50年中，BNB生物学在健康和疾病方面的重大进步受到了限制。在正常和病理性人类周围神经的转录组和蛋白质组学研究的指导下，从特征明确的外周神经病患者中纯化形成的BNB和白细胞的原代和永生化的人神经内膜内皮细胞，通过原位或离体蛋白质表达研究的验证，有关人类BNB在健康和特定周围神经病以及慢性神经性疼痛中的分子和功能特征的数据正在涌现。这些早期的进展不仅有可能增进我们对BNB如何工作以及如何适应或不能适应各种损伤的理解，而且还提供与致病性白细胞运输有关的见解，具有转化潜力以及对慢性周围神经病和神经性疼痛的特殊治疗应用。