Bulnes S, Bilbao J, Lafuente J V
Laboratory of Clinical and Experimental Neuroscience (LaNCE), Department of Neuroscience, Basque Country University, Leioa, Spain.
Histol Histopathol. 2009 Jun;24(6):693-706. doi: 10.14670/HH-24.693.
Glioma growth depends on microvascular adaptation and angiogenesis. Our study focused on the structural changes that occur in the microvasculature to adapt to glioma growth. Vascular morphology, morphometry and permeability studies were performed in induced rat gliomas. Tumours were identified by magnetic resonance imaging and histopathology. Blood brain barrier integrity was examined by EBA and GluT-1 immunostaining and correlated with vascular permeability for gadolinium and intravital dyes. VEGF165 immunoexpression was also analyzed. Tumours were grouped in microtumours (6.69+/-0.99 mm3) displaying a homogeneous T2-w hyperintense signal corresponding to low-grade gliomas, and macrotumours (900.79+/-332.39 mm3) showing gadolinium contrast enhancement, intravital dye extravasation and histopathological features of high-grade gliomas. Results show that the microvascular network becomes aberrant as we move from micro to macrotumours. Vessel density decreases, whereas the relative area occupied by the vascular network increases. Microtumours display homogeneous angioarchitecture composed of simple and mildly dilated vessels similar to normal tissue. Macrotumours show different patterns, following a gradient from the neoangiogenic border to the hypoxic core. The tumour core contains scarce, huge, dilated vessels with some profiles co-expressing GluT-1 and VEGF165, the peripheral tissue shows light dilated vessels co-expressing EBA and GluT-1, and the border area displays glomeruloid vessels strongly positive for VEGF. Glucose uptake was maintained for some vascular endothelial sections in areas where BBB function was lost. In conclusion, during development of gliomas the microvasculature becomes aberrant, undergoing a sequence of adaptive changes which involve the distribution and permeability of vessels. This explains the disturbances of blood flow and the increased permeability.
胶质瘤的生长依赖于微血管适应和血管生成。我们的研究聚焦于微血管系统为适应胶质瘤生长而发生的结构变化。对诱导产生的大鼠胶质瘤进行了血管形态、形态测量及通透性研究。通过磁共振成像和组织病理学鉴定肿瘤。采用伊文思蓝白蛋白（EBA）和葡萄糖转运蛋白-1（GluT-1）免疫染色检测血脑屏障完整性，并将其与钆和活体染料的血管通透性相关联。还分析了血管内皮生长因子165（VEGF165）的免疫表达。将肿瘤分为微肿瘤（体积为6.69±0.99立方毫米），其呈现均匀的T2加权高信号，对应低级别胶质瘤；以及大肿瘤（体积为900.79±332.39立方毫米），其显示钆对比增强、活体染料外渗及高级别胶质瘤的组织病理学特征。结果表明，随着从微肿瘤发展到大肿瘤，微血管网络变得异常。血管密度降低，而血管网络所占相对面积增加。微肿瘤呈现由类似于正常组织的简单且轻度扩张的血管组成的均匀血管构筑。大肿瘤呈现不同模式，从新生血管形成边界到缺氧核心呈梯度变化。肿瘤核心包含稀少、巨大、扩张的血管，部分血管同时表达GluT-1和VEGF165；周边组织显示轻度扩张的血管同时表达EBA和GluT-1；边界区域呈现对VEGF呈强阳性的肾小球样血管。在血脑屏障功能丧失的区域，一些血管内皮切片仍维持葡萄糖摄取。总之，在胶质瘤发展过程中，微血管系统变得异常，经历一系列适应性变化，包括血管的分布和通透性。这解释了血流紊乱和通透性增加的现象。
