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Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain

机译：成年小鼠大脑感觉性脑室的异质性血管通透性和替代扩散障碍

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摘要

Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB.
机译：感觉性室间隔器官（CVO）的有毛细血管，包括椎板终末的输精管，耻骨下器官和视网膜后区域，缺乏血脑屏障（BBB）的完整性，无法感测各种血源性分子并将信息传递到其他大脑区域。我们检查了血源性分子的血管通透性和感觉CVO中紧密连接蛋白的表达。目前的示踪剂分析显示，分子量（MW）为10,000的源自血液的右旋糖酐10 k（Dex10k）保留在内和外基底膜之间的血管周围空间中，但异硫氰酸荧光素（FITC; MW：389）和Dex3k（ MW：3000）扩散到实质中。 FITC的血管通透性在中央分支高于远侧分支。 FITC和Dex3k均未扩散到神经胶质原纤维酸性蛋白（GFAP）阳性星形胶质细胞/单核细胞的致密网络之外。在感觉CVO的中央部分无法检测到紧密连接蛋白（例如，闭合蛋白，claudin-5和小带闭合蛋白1（ZO-1））的表达，但有些表达在远端的CVO中。电子显微镜观察表明，毛细血管被许多星形胶质细胞突和树突包围。还观察到了occludin和ZO-1的表达在感觉CVO的GFAP阳性星形胶质细胞/单核细胞上呈点状。因此，我们的研究证明了血管通透性和紧密连接蛋白表达的异质性，并表明外基底膜和密集的星形胶质细胞/单核细胞连接可能是替代血源性分子而不是血脑屏障的替代机制。

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