Neuromuscular Immunopathology Research Laboratory, Division of Neuromuscular Disease, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama.
J Peripher Nerv Syst. 2019 Jun;24(2):195-206. doi: 10.1111/jns.12326. Epub 2019 Jun 4.
The blood-nerve barrier (BNB) formed by tight junction-forming endoneurial microvessels located in the innermost compartment of peripheral nerves, and the perineurium serve to maintain the internal microenvironment required for normal signal transduction. The specific molecular components that define the normal adult human BNB are not fully known. Guided by data derived from the adult human BNB transcriptome, we evaluated the in situ expression of 25 junctional complex, transporter, cell membrane, and cytoskeletal proteins in four histologically normal adult sural nerves by indirect fluorescent immunohistochemistry to determine proteins specifically expressed by restrictive endoneurial microvascular endothelium. Using Ulex Europaeus Agglutinin-1 expression to detect endothelial cells, we ascertained that the selected proteins were uniformly expressed in ≥90% of endoneurial microvessels. P-glycoprotein (also known as adenosine triphosphate-binding cassette subfamily B member 1) and solute carrier family 1 member 1 demonstrated restricted expression by endoneurial endothelium only, with classic tight junction protein claudin-5 also expressed on fenestrated epineurial macrovessels, and vascular-specific adherens junction protein cadherin-5 also expressed by the perineurium. The expression profiles of the selected proteins provide significant insight into the molecular composition of normal adult peripheral nerves. Further work is required to elucidate the human adult BNB molecular signature in order to better understand its development and devise strategies to restore function in peripheral neuropathies.
血-神经屏障 (BNB) 由位于周围神经最内层的紧密连接形成的神经内膜微血管和神经外膜形成，用于维持正常信号转导所需的内部微环境。定义正常成人 BNB 的特定分子成分尚不完全清楚。根据成人 BNB 转录组的数据，我们通过间接荧光免疫组织化学评估了 25 种连接复合体、转运蛋白、细胞膜和细胞骨架蛋白在 4 根组织学正常成人腓肠神经中的原位表达，以确定限制神经内膜微血管内皮细胞特异性表达的蛋白。使用荆豆凝集素-1 表达来检测内皮细胞，我们确定所选蛋白在神经内膜微血管中≥90%的内皮细胞中均匀表达。P 糖蛋白（也称为三磷酸腺苷结合盒亚家族 B 成员 1）和溶质载体家族 1 成员 1仅由神经内膜内皮细胞受限表达，经典紧密连接蛋白 Claudin-5 也在有孔神经外膜大血管上表达，血管特异性黏着连接蛋白 Cadherin-5 也由神经外膜表达。所选蛋白的表达谱为正常成人周围神经的分子组成提供了重要的见解。需要进一步的工作来阐明人类成人 BNB 的分子特征，以便更好地了解其发育并制定策略来恢复周围神经病变的功能。
