Development of blood-brain barrier tight junctions in the rat cortex
Development of blood-brain barrier tight junctions in the rat cortex
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DOI：
10.1016/0165-3806(96)00117-4
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发表时间：
1996-10-23
期刊：
影响因子：
--
通讯作者：
Wolburg, H
中科院分区：
文献类型：
--
作者：
Kniesel, U;Risau, W;Wolburg, H
血脑屏障的结构相当于脑毛细血管内皮细胞之间的复杂紧密连接(TJ)。本研究采用冷冻断裂技术，定量研究了大鼠大脑皮质发育过程中血脑屏障内皮细胞TJs精细结构的变化。在胚胎第13天、第15天、第18天、出生后第1天和成体，评价TJ网络的复杂性、TJ链的完整性和TJ颗粒与膜双层原生质叶的结合程度(占TJ总长度的百分比)。我们观察到，在E18和P1之间，TJ网络的整体复杂性和TJ颗粒的P面关联显著增加。这两个TJ参数的增加与E18开始的粒子完全插入相结合，可能反映了血脑屏障向成熟状态过渡的过程，这一过程具有TJ的高度复杂性和TJ粒子的P面关联的优势，并与先前的生理测量密切相关，如跨内皮细胞电阻。在E15和E18可区分出TJ颗粒密度不同的两个种群，这表明TJ组装是一种非线性的异步机制。Al E13，无颗粒膜专化排列成TJ样图案，与TJ特有的槽和脊非常相似。在低钙条件下培养的脑内皮细胞也得到了类似的结果，这表明钙粘附素/连环蛋白复合体参与了TJ的调节。无颗粒的‘TJ前体’强烈地表明，在TJ颗粒出现在其连接内位置之前，已经建立了与TJ相关的细胞骨架网络。
The structural equivalent of the blood-brain barrier are the complex tight junctions (TJs) between endothelial cells of brain capillaries. In this study, we have quantitatively investigated by the freeze-fracture technique the modulation of the fine structure of TJs in blood-brain barrier endothelial cells during development of the rat cerebral cortex. The complexity of the TJ network as defined by fractal dimension, the integrity of TJ strands and the degree of TJ particle association to the protoplasmic leaflet of the membrane bilayer in percent of total TJ length were evaluated at embryonic days (E) 13, 15, 18, postnatal day (P) 1 and adult. We observed that the overall complexity of the TJ network and P-face association of TJ particles are significantly increased between E18 and P1. The increase in both of these TJ parameters in combination with the completed particle insertion starting from E18 is likely to reflect the process of transition to the mature state of the blood-brain barrier, which is characterized by high complexity of TJs and predominance of P-face association of TJ particles and correlated tightly with previous physiological measurements, e.g. transendothelial electrical resistance. Two populations of TJs differing in TJ particle density were distinguishable at E15 and E18, which indicates a non-linear asynchronous mechanism of TJ assembly. Al E13, particle-free membrane specializations arranged in a TJ-like pattern strongly resembled TJ specific grooves and ridges. Similar results were obtained from cultures of brain endothelial cells in the presence of low calcium conditions, which suggests the involvement of the cadherin/catenin complex in TJ regulation. The particle-free 'TJ precursors' strongly indicate an established TJ associated cytoskeletal network before the TJ particles are present in their intra-junctional location.