Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice.
Outflow of cerebrospinal fluid is predominantly through lymphatic vessels and is reduced in aged mice.
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DOI：
10.1038/s41467-017-01484-6
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发表时间：
2017-11-10
影响因子：
16.6
通讯作者：
Proulx ST
中科院分区：
文献类型：
--
作者：
Ma Q;Ineichen BV;Detmar M;Proulx ST
脑脊液（CSF）通常被认为是通过蛛网膜突出物从蛛网膜下腔引流到硬膜静脉窦。然而，CSF流出的淋巴成分早已为人所知。在这里，我们利用荧光报告小鼠和高分辨率立体显微镜来表征脑脊液流出的解剖途径和动力学。注入侧脑室后，示踪剂扩散到软脑膜和大脑皮质的血管旁间隙。示踪剂还通过颅骨中的孔使用神经周路径快速到达淋巴结。使用非侵入性成像技术，可以量化的示踪剂的运输到血液和淋巴结，我们发现，淋巴管的主要流出途径，为大分子和小分子示踪剂在小鼠。与年轻小鼠相比，老年小鼠的CSF淋巴流出量显著下降，表明淋巴系统可能是年龄相关神经系统疾病的靶点。据信，大部分脑脊液（CSF）通过蛛网膜突起从蛛网膜下腔引流到硬脑膜静脉窦。在这里，作者表明，小鼠中CSF的主要流出途径是淋巴管，并且这种引流随着小鼠年龄的增长而减少。
Cerebrospinal fluid (CSF) has been commonly accepted to drain through arachnoid projections from the subarachnoid space to the dural venous sinuses. However, a lymphatic component to CSF outflow has long been known. Here, we utilize lymphatic-reporter mice and high-resolution stereomicroscopy to characterize the anatomical routes and dynamics of outflow of CSF. After infusion into a lateral ventricle, tracers spread into the paravascular spaces of the pia mater and cortex of the brain. Tracers also rapidly reach lymph nodes using perineural routes through foramina in the skull. Using noninvasive imaging techniques that can quantify the transport of tracers to the blood and lymph nodes, we find that lymphatic vessels are the major outflow pathway for both large and small molecular tracers in mice. A significant decline in CSF lymphatic outflow is found in aged compared to young mice, suggesting that the lymphatic system may represent a target for age-associated neurological conditions. It is believed that the bulk of cerebrospinal fluid (CSF) drains through arachnoid projections from the subarachnoid space to the dural venous sinuses. Here the authors show that the major outflow pathway for CSF in mice are lymphatic vessels and that this drainage decreases as the mice age.