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将肠道神经胶质细胞移植到大鼠脊髓后血脑屏障形成的加速

Acceleration of blood-brain barrier formation after transplantation of enteric glia into spinal cords of rats.

作者信息

Jiang Shucui, Khan Mohammad I, Lu Yao, Werstiuk Eva S, Rathbone Michel P

机构信息

Department of Medicine, McMaster University, Health Sciences Centre 4N71, 1200 Main Street West, Hamilton, ON, L8N 3Z5, Canada.

出版信息

Exp Brain Res. 2005 Mar;162(1):56-62. doi: 10.1007/s00221-004-2119-3. Epub 2004 Dec 15.

DOI:10.1007/s00221-004-2119-3
PMID:15599730
Abstract

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.

摘要

肠神经胶质细胞与星形胶质细胞具有相似的形态、生化和功能特性。因此,与星形胶质细胞一样,将肠神经胶质细胞移植到中枢神经系统(CNS)中可能会促进内皮细胞中血脑屏障(BBB)特性的发展。本研究通过检查植入大鼠脊髓后的屏障形成情况来探索这种可能性。将菜豆白细胞凝集素(PHAL)处理过的肠神经胶质细胞悬液注射到成年雌性Wistar大鼠T11 - T12水平的脊髓中。对照动物注射3T3成纤维细胞、胶质瘤C6细胞或培养基。在植入后1周到2个月期间,从静脉注射伊文思蓝,这是一种血脑屏障可排除的染料。通过肉眼观察染料渗漏情况,并检查毛细血管的超微结构。在第一周,染料渗漏在超微结构上主要与内皮细胞非重叠连接相关,甚至相邻细胞之间存在裂隙。紧密连接在2个月时完全形成,没有染料渗漏。电子显微镜分析表明,肠神经胶质细胞的终足与内皮细胞紧密接触。相比之下,所有对照动物的注射部位在2个月前都有染料渗漏,并且形成的大多数紧密连接都是不完整的。此外,大多数3T3或C6对照细胞在2个月时已经死亡,存活下来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,植入肠神经胶质细胞可加速脊髓毛细血管中血脑屏障特性的形成。

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