Laboratory of Psychiatry and Exp. Alzheimer's Research, Department of Psychiatry and Psychotherapy, Innsbruck Medical University, Austria.
Curr Neurovasc Res. 2010 Aug;7(3):192-200. doi: 10.2174/156720210792231787.
Increased homocysteine (Hcy) levels contribute to a variety of cardiovascular and cerebrovascular diseases including stroke and Alzheimer's disease. Recent data has shown that elevated levels of Hcy can lead to the blood-brain barrier (BBB) dysfunction and activation. However, the mechanism for Hcy-mediated dysfunction remains unclear. The aim of this study is to characterize the effects of moderate Hcy administration in rat brain capillary endothelial cells (BCECs), which serve as a simple model to study blood-brain barrier (BBB) functions. This present study shows that addition of 20 microM Hcy for 6 days did not significantly affect BCEC survival, as measured by acridine orange staining, propidium iodide staining, and nitrite content. However, addition of 20 microM Hcy for 6 days did elevate lactate dehydrogenase (LDH) activity released into the supernatant of BCECs, as well as significantly enhance the transmigration of monocytes across the BCEC in a time-dependent manner. In addition, TNFalpha levels in BCEC were also elevated by Hcy, whereas inflammatory markers MIP3alpha and RANTES were significantly reduced. Finally, this study also shows that intercellular adhesion molecule-1 (ICAM-1) expression is significantly enhanced by 20 microM Hcy treatment compared to control conditions. These results suggest that moderate levels of homocysteine can affect proinflammatory patterns expressed by BCECs ultimately leading to BBB activation and dysfunction through enhanced monocyte transmigration and ICAM-1 expression.
同型半胱氨酸（Hcy）水平升高可导致多种心血管和脑血管疾病，包括中风和阿尔茨海默病。最近的数据表明，Hcy 水平升高可导致血脑屏障（BBB）功能障碍和激活。然而，Hcy 介导的功能障碍的机制尚不清楚。本研究旨在描述中度 Hcy 给药对大鼠脑毛细血管内皮细胞（BCEC）的影响，BCEC 可作为研究血脑屏障（BBB）功能的简单模型。本研究表明，添加 20μM Hcy 6 天不会显著影响 BCEC 的存活，用吖啶橙染色、碘化丙啶染色和亚硝酸盐含量来衡量。然而，添加 20μM Hcy 6 天会增加 BCEC 上清液中乳酸脱氢酶（LDH）的活性，并显著增强单核细胞穿过 BCEC 的迁移，呈时间依赖性。此外，Hcy 还可使 BCEC 中的 TNFalpha 水平升高，而炎症标志物 MIP3alpha 和 RANTES 则显著降低。最后，本研究还表明，与对照条件相比，20μM Hcy 处理可显著增强细胞间黏附分子-1（ICAM-1）的表达。这些结果表明，中度同型半胱氨酸水平可影响 BCEC 表达的促炎模式，最终通过增强单核细胞迁移和 ICAM-1 表达导致 BBB 激活和功能障碍。
