Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.
Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI.
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DOI：
10.7554/elife.29738
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发表时间：
2017-10-03
期刊：
影响因子：
7.7
通讯作者：
Reich DS
中科院分区：
文献类型：
--
作者：
Absinta M;Ha SK;Nair G;Sati P;Luciano NJ;Palisoc M;Louveau A;Zaghloul KA;Pittaluga S;Kipnis J;Reich DS
在这里，我们报告的存在脑膜淋巴管在人类和非人类灵长类动物（常见的绒猴）和非侵入性成像和映射它们在体内的高分辨率，临床MRI的可行性。在T2-FLAIR和T1加权黑血成像中，淋巴管在钆布醇（一种钆基造影剂，具有高渗透性毛细血管内皮屏障外渗倾向）的作用下增强，但在钆磷维塞（一种血池造影剂）的作用下则无此现象。这些血管沿着硬脑膜静脉窦的地形，重现了啮齿动物的脑膜淋巴系统。在灵长类动物中，脑膜炎通过免疫组织化学显示出一组典型的淋巴管内皮标志物。这一发现为更好地理解中枢神经系统淋巴引流的正常生理学和神经系统疾病中的潜在畸变提供了希望。大脑是如何清除废物的？身体的其他器官通过一个称为淋巴系统的系统来实现这一点。淋巴管网络以类似于血管的模式延伸到全身。细胞产生的废物，加上细菌，病毒和多余的液体从身体组织排出到淋巴管，淋巴管将它们转移到血液中。然后，血管将废物运送到肾脏，肾脏将其过滤并排泄。淋巴管也是白色血细胞循环的高速公路，白细胞对抗感染，因此是免疫系统的重要组成部分。与其他器官不同，大脑不包含淋巴管。那么，它是如何去除废物的呢？大脑的一些废物进入了保护大脑的液体-脑脊液-然后通过血液被处理掉。然而，最近对啮齿动物的研究也表明，在大脑周围的外膜（硬脑膜）内存在淋巴管。Absinta，Ha等人现在表明，人类和绒猴的硬脑膜也含有淋巴管。发现淋巴管是具有挑战性的，因为它们类似于血管，而血管要多得多。此外，Absinta，Ha等人发现了一种使用脑磁共振成像可视化硬脑膜中淋巴管的方法，并可以使用特殊染色方法确认淋巴管存在于尸检组织中。为了进行磁共振成像，猴子和人类志愿者接受了一种名为钆的染料样物质的注射，这种物质通过血液进入大脑。在硬脑膜中，钆从血管中泄漏出来，聚集在淋巴管中，在大脑扫描中显示为明亮的白色区域。为了确认白色区域是淋巴管，使用不会从血管中漏出的不同染料重复实验。正如预期的那样，在之前的大脑扫描中观察到的信号并没有出现。通过可视化淋巴系统，这项技术使研究大脑如何清除废物和循环白色血细胞成为可能，并检查这一过程是否在衰老或疾病中受损。
Here, we report the existence of meningeal lymphatic vessels in human and nonhuman primates (common marmoset monkeys) and the feasibility of noninvasively imaging and mapping them in vivo with high-resolution, clinical MRI. On T2-FLAIR and T1-weighted black-blood imaging, lymphatic vessels enhance with gadobutrol, a gadolinium-based contrast agent with high propensity to extravasate across a permeable capillary endothelial barrier, but not with gadofosveset, a blood-pool contrast agent. The topography of these vessels, running alongside dural venous sinuses, recapitulates the meningeal lymphatic system of rodents. In primates, meningeal lymphatics display a typical panel of lymphatic endothelial markers by immunohistochemistry. This discovery holds promise for better understanding the normal physiology of lymphatic drainage from the central nervous system and potential aberrations in neurological diseases. How does the brain rid itself of waste products? Other organs in the body achieve this via a system called the lymphatic system. A network of lymphatic vessels extends throughout the body in a pattern similar to that of blood vessels. Waste products from cells, plus bacteria, viruses and excess fluids drain out of the body’s tissues into lymphatic vessels, which transfer them to the bloodstream. Blood vessels then carry the waste products to the kidneys, which filter them out for excretion. Lymphatic vessels are also a highway for circulation of white blood cells, which fight infections, and are therefore an important part of the immune system. Unlike other organs, the brain does not contain lymphatic vessels. So how does it remove waste? Some of the brain’s waste products enter the fluid that bathes and protects the brain – the cerebrospinal fluid – before being disposed of via the bloodstream. However, recent studies in rodents have also shown the presence of lymphatic vessels inside the outer membrane surrounding the brain, the dura mater. Absinta, Ha et al. now show that the dura mater of people and marmoset monkeys contains lymphatic vessels too. Spotting lymphatic vessels is challenging because they resemble blood vessels, which are much more numerous. In addition, Absinta, Ha et al. found a way to visualize the lymphatic vessels in the dura mater using brain magnetic resonance imaging, and could confirm that lymphatic vessels are present in autopsy tissue using special staining methods. For magnetic resonance imaging, monkeys and human volunteers received an injection of a dye-like substance called gadolinium, which travels via the bloodstream to the brain. In the dura mater, gadolinium leaks out of blood vessels and collects inside lymphatic vessels, which show up as bright white areas on brain scans. To confirm that the white areas were lymphatic vessels, the experiment was repeated using a different dye that does not leak out of blood vessels. As expected, the signals observed in the previous brain scans did not appear. By visualizing the lymphatic system, this technique makes it possible to study how the brain removes waste products and circulates white blood cells, and to examine whether this process is impaired in aging or disease.