Defective Function of the Blood?Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model
Defective Function of the Blood?Brain Barrier in a Stroke-Prone Spontaneously Hypertensive Rat: Evaluation in an In Vitro Cell Culture Model
复制标题
易中风自发性高血压大鼠的血脑屏障功能缺陷：体外细胞培养模型的评估
DOI：
10.1007/s10571-020-00917-z
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发表时间：
2020
影响因子：
4
通讯作者：
Nabika Toru
中科院分区：
文献类型：
--
作者：
Nakagawa Shinsuke;Ohara Hiroki;Niwa Masami;Yamagata Kazuo;Nabika Toru
血脑屏障 (BBB) 包含三种细胞类型：脑毛细血管内皮细胞 (BEC)、星形胶质细胞和周细胞。这些细胞之间的异常相互作用可能会引起血脑屏障功能障碍并导致脑血管疾病。易发生中风的自发性高血压大鼠 (SHRSP) 存在有缺陷的 BBB，因此我们设计本研究来检查这三种细胞类型在 SHRSP 中 BBB 功能障碍中的作用，以便更广泛地阐明这些细胞在 BBB 中的作用。为此，我们采用了独特的 BBB 体外模型，可以在其中测试细胞的各种组合。这三种类型的细胞均由 SHRSP 和 Wistar 京都大鼠 (WKY) 制备。然后将它们以各种组合共培养以构建体外 BBB 模型。通过测量跨内皮电阻和内皮单层对荧光素钠的渗透性来评估模型的屏障功能。体外模型显示，(1) SHRSP 的 BEC 具有固有的较低屏障功能，(2) SHRSP 的星形胶质细胞诱导 BEC 屏障功能的能力受损，尽管 (3) SHRSP 和 WKY 的周细胞和星形胶质细胞都可以在共培养条件下增强 BEC 的屏障功能。此外，我们发现在使用 BEC 和/或 SHRSP 星形胶质细胞的模型中，claudin-5 表达始终较低。这些结果表明，BBB 细胞（尤其是 BEC 和星形胶质细胞）之间的相互作用缺陷是 SHRSP 中 BBB 功能障碍的原因。
The blood–brain barrier (BBB) comprises three cell types: brain capillary endothelial cells (BECs), astrocytes, and pericytes. Abnormal interaction among these cells may induce BBB dysfunction and lead to cerebrovascular diseases. The stroke-prone spontaneously hypertensive rat (SHRSP) harbors a defective BBB, so we designed the present study to examine the role of these three cell types in a functional disorder of the BBB in SHRSP in order to elucidate the role of these cells in the BBB more generally. To this end, we employed a unique in vitro model of BBB, in which various combinations of the cells could be tested. The three types of cells were prepared from both SHRSPs and Wistar Kyoto rats (WKYs). They were then co-cultured in various combinations to construct in vitro BBB models. The barrier function of the models was estimated by measuring transendothelial electrical resistance and the permeability of the endothelial monolayer to sodium fluorescein. The in vitro models revealed that (1) BECs from SHRSPs had an inherent lower barrier function, (2) astrocytes of SHRSPs had an impaired ability to induce barrier function in BECs, although (3) both pericytes and astrocytes of SHRSPs and WKYs could potentiate the barrier function of BECs under co-culture conditions. Furthermore, we found that claudin-5 expression was consistently lower in models that used BECs and/or SHRSP astrocytes. These results suggested that defective interaction among BBB cells—especially BECs and astrocytes—was responsible for a functional disorder of the BBB in SHRSPs.