Effects of lipopolysaccharide on the radiation-induced changes in the blood-brain barrier and the astrocytes
Effects of lipopolysaccharide on the radiation-induced changes in the blood-brain barrier and the astrocytes
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DOI：
10.1016/j.brainres.2004.05.102
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发表时间：
2004-09-03
期刊：
影响因子：
2.9
通讯作者：
Karadeniz, A
中科院分区：
文献类型：
--
作者：
Kaya, M;Palanduz, A;Karadeniz, A
使用放射来提高化疗对恶性脑肿瘤的疗效也已知会对大脑正常部位的血管内皮细胞和星形胶质细胞产生副作用。本研究观察了脂多糖（LPS）对大鼠全脑照射后血脑屏障（BBB）功能、结构和星形胶质细胞活性的影响。照射后大鼠大脑皮质、间脑和小脑区血脑屏障对伊文思蓝（EB）染料的通透性明显增加（P < 0.01）。而LPS则使照射后大鼠血脑屏障通透性明显降低（P < 0.05）。肿瘤坏死因子-α（TNF-α）在LPS、照射及照射加LPS后均明显升高（P < 0.05，P < 0.01）。照射后的脑血管显示紧密连接蛋白ZO-1和occludin的染色强度明显降低。在用LPS和照射加LPS处理的动物中，封闭带-1和occludin的染色是密集的。胶质细胞酸性蛋白（GFAP）的免疫反应被认为是在极少数的星形胶质细胞照射的大脑。然而，这种染色显示在LPS处理的脑切片以及照射加LPS处理的动物中阳性强度增加。这些结果表明，LPS减少通过外源性血管示踪剂EB-结合白蛋白进入大脑，至少部分，通过增加紧密连接蛋白和GFAP的表达，照射后。我们认为，辐射可能会影响细胞旁的通透性，通过破坏紧密连接蛋白，封闭带-1和occludin，和LPS可以提供有益的影响，对血脑屏障的完整性和星形胶质细胞对辐射损伤。(C)2004 Elsevier B. V.保留所有权利。
The use of radiation to improve the efficacy of chemotherapy on malignant brain tumors is also known to cause side effects on vascular endothelial cells and astrocytes in normal parts of the brain. We investigated the effects of lipopolysaccharide (LPS) on the functional and structural properties of blood-brain barrier (BBB) and the activity of astrocytes during whole-brain irradiation in rats. The permeability of the BBB to Evans blue (EB) dye significantly increased in the cerebral cortex, diencephalon and cerebellum regions of rats exposed to irradiation (P < 0.01). In contrast, the BBB permeability in irradiated rats was significantly reduced by LPS (P < 0.05). Tumor necrosis factor-alpha (TNF-alpha) levels were increased following LPS, irradiation and irradiation plus LPS (P < 0.05, P < 0.01). Irradiated brain vessels showed a considerable loss of staining intensity of tight junction proteins Zonula occludens-1 (ZO-1) and occludin. Staining for Zonula occludens-1 and occludin was intensive in animals treated with LPS and irradiation plus LPS. Glial fibrillary acidic protein (GFAP) immunoreactivity was seen in very few astrocytes of irradiated brains. However, this staining showed an increased positive intensity in the brain sections of LPS-treated as well as of irradiation plus LPS-treated animals. These results indicate that LPS reduces the passage of exogenous vascular tracer EB-binding albumin into the brain, at least partly, by increasing the expression of tight junction proteins and GFAP, following the irradiation. We suggest that irradiation may affect paracellular permeability through disruption of tight junction proteins, Zonula occludens-1 and occludin, and LPS could provide beneficial effects on the BBB integrity and the astrocytes against irradiation damage. (C) 2004 Elsevier B.V. All rights reserved.