Acceleration of blood-brain barrier formation after transplantation of enteric glia into spinal cords of rats
Acceleration of blood-brain barrier formation after transplantation of enteric glia into spinal cords of rats
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DOI：
10.1007/s00221-004-2119-3
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发表时间：
2005-03-01
影响因子：
2
通讯作者：
Rathbone, M
中科院分区：
文献类型：
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作者：
Jiang, S;Khan, M;Rathbone, M
肠神经胶质细胞与星形胶质细胞具有相同的形态、生化和功能特性。因此，与星形胶质细胞一样，肠胶质细胞移植到中枢神经系统（CNS）中可能有助于内皮细胞中血脑屏障（BBB）特征的发育。本研究通过检查植入大鼠脊髓后屏障的形成来探索这种可能性。将菜豆白细胞凝集素（PHAL）处理的肠胶质细胞悬液注射到成年Wistar雌性大鼠的T11-T12脊髓水平。对照动物注射3 T3成纤维细胞、胶质瘤C6细胞或培养基。植入后1周至2个月静脉注射伊文思蓝（一种被BBB排除的染料）。通过肉眼观察确定染料渗漏，并检查毛细血管的超微结构。在第一周的染料泄漏相关的超微结构与主要是非重叠的内皮细胞连接，甚至与相邻细胞之间的裂缝。2个月时完全形成紧密连接，无染料泄漏。电镜分析显示肠神经胶质细胞具有与内皮细胞紧密接触的终足。相比之下，所有对照动物的注射部位渗漏染料，直至2个月，并且形成的大部分紧密连接不完整。此外，大多数3 T3或C6对照细胞在2个月时死亡，而那些存活的细胞与肠神经胶质细胞不同，与血管没有解剖学关系。这些数据表明，肠神经胶质细胞的植入加速了脊髓毛细血管中BBB特征的形成。
Enteric glia share morphological, biochemical, and functional properties with astrocytes. Thus, like astrocytes, transplantation of enteric glia into the central nervous system (CNS) might facilitate the development of the characteristics of the blood brain barrier (BBB) in endothelial cells. This study explored this possibility by examining barrier formation after implantation into the spinal cord of rats. Phaseolus vulgaris leucoagglutin (PHAL)-treated enteric glia suspensions were injected into the spinal cord at the T11-T12 level of adult Wistar female rats. Control animals were injected with either 3T3 fibroblast, glioma C6 cells, or culture medium. Evan's blue, a dye excluded by the BBB, was injected intravenously from 1 week to 2 months after implantation. Leakage of dye was determined macroscopically and the ultrastructure of the capillaries was examined. During the first week leakage of dye correlated ultrastructurally with predominantly non-overlapping endothelial cell junctions, even with clefts between adjacent cells. Tight junctions were fully formed by 2 months and no dye leaked. Electron microscopic analysis showed that enteric glia had end-feet in close contact with endothelial cells. In contrast, the injection sites in all control animals leaked dye until 2 months, and most of the tight junctions that did form were incomplete. Furthermore, most 3T3 or C6 control cells had died at 2 months and those that survived, unlike enteric glia, had no anatomical relationship to blood vessels. These data demonstrate that implantation of enteric glia accelerates the formation of the characteristics of the BBB in spinal cord capillaries.