Laboratory of Pathoneurochemistry, Department of Neurochemistry, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str., 02-106 Warsaw, Poland.
Electron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego str., 02-106 Warsaw, Poland.
Toxicology. 2018 Sep 1;408:31-38. doi: 10.1016/j.tox.2018.06.009. Epub 2018 Jun 20.
The widespread use of silver nanoparticles (AgNPs) in medicine and in multiple commercial products has motivated researchers to investigate their potentially hazardous effects in organisms. Since AgNPs may easily enter the brain through the blood-brain barrier (BBB), characterization of their interactions with cellular components of the neurovascular unit (NVU) is of particular importance. Therefore, in an animal model of prolonged low-dose exposure, we investigate the extent and mechanisms of influence of AgNPs on cerebral microvessels. Adult rats were treated orally with small (10 nm) AgNPs in a dose of 0.2 mg/kg b.w. over a 2-week period. A silver citrate-exposed group was established as a positive control of ionic silver effects. Alterations in the expression of tight junction proteins claudin-5, ZO-1, and occludin, were observed. These effects are accompanied by ultrastructural features indicating enhanced permeability of microvessels such as focal edema of perivascular astrocytic processes and surrounding neuropil. We did not identify changes in the expression of PDGFβR which is a marker of pericytes. Ultrastructural alterations in these cells were not identified. The results show that altered integrity of cerebral vessels under a low-dose of AgNP-exposure may be the consequence of dysfunction of endothelial cells caused by disruption of tight junction proteins.
由于银纳米粒子（AgNPs）在医学和多种商业产品中的广泛应用，促使研究人员研究其在生物体中潜在的有害影响。由于 AgNPs 可能很容易通过血脑屏障（BBB）进入大脑，因此研究它们与神经血管单元（NVU）的细胞成分相互作用的特性尤为重要。因此，在长期低剂量暴露的动物模型中，我们研究了 AgNPs 对大脑微血管的影响程度和机制。成年大鼠经口给予小（10nm）AgNPs，剂量为 0.2mg/kg b.w.，持续 2 周。建立了银柠檬酸盐暴露组作为离子银作用的阳性对照。观察到紧密连接蛋白 Claudin-5、ZO-1 和 Occludin 的表达发生改变。这些作用伴随着微血管通透性增强的超微结构特征，例如血管周星形胶质细胞突起和周围神经组织的局灶性水肿。我们没有发现 PDGFβR（周细胞的标志物）表达的变化。这些细胞的超微结构改变没有被识别。结果表明，低剂量 AgNP 暴露下脑血管完整性的改变可能是由于紧密连接蛋白的破坏导致内皮细胞功能障碍的结果。
