Is there a cerebral lymphatic system?
Is there a cerebral lymphatic system?
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DOI：
10.1161/strokeaha.112.678698
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发表时间：
2013-06
期刊：
影响因子：
8.3
通讯作者：
Nedergaard M
中科院分区：
文献类型：
--
作者：
Iliff JJ;Nedergaard M
正如我们最近的研究中所详述的那样，这些发现表明，aqp4依赖的大流量将脑脊液沿动脉旁途径流入，沿静脉旁途径清除ISF，形成一个全器官系统，促进脑实质间质溶质的清除。基于这种胶质依赖性以及与外周淋巴系统的功能和结构同源性，我们将这种胶质-血管通路称为淋巴系统（图1A）。可溶性淀粉样蛋白β (Aβ)存在于健康年轻大脑的ISF中，而Aβ清除的失败被认为是与阿尔茨海默病进展相关的Aβ斑块沉积的基础。10,11接下来，我们评估了可溶性Aβ是否构成沿淋巴通路从脑间质清除的溶质之一。当荧光标记的Aβ注射到皮层或纹状体时，它在其他荧光示踪剂观察到的相同的血管旁通路周围积累。我们还测量了直接注射到野生型和aqp4缺失小鼠纹状体中的放射性标记的Aβ的清除率。在aqp4缺失的小鼠中，与野生型小鼠相比，放射性标记的Aβ清除率降低了约65%，这表明aqp4依赖的大体积流动沿着神经通路
As detailed in our recent study, 14 these findings demonstrate that AQP4-dependent bulk flow couples CSF influx along the para-arterial pathway to ISF clearance along the paravenous route, forming an organ-wide system that facilitates the clearance of interstitial solutes from the brain parenchyma. On the basis of this glial dependence and the functional and structural homology to the peripheral lymphatic system, we have termed this glio-vascular pathway the glymphatic system (Figure 1A).Soluble amyloid β (Aβ) is present in the ISF of the healthy young brain and the failure of Aβ clearance is thought to underlie the deposition of Aβ plaques associated with Alzheimer disease progression. 10, 11 We next evaluated whether soluble Aβ constitutes one of the solutes cleared from the brain interstitium along the glymphatic pathway. When fluorescently labeled Aβ was injected into the cortex or striatum, it accumulated around the same paravascular pathways observed with other fluorescent tracers. 14 We also measured the clearance of radiolabeled Aβ injected directly into the striatum of wildtype and Aqp4-null mice. In Aqp4-null mice, radiolabeled Aβ clearance was reduced by≈ 65% compared with wild-type mice, suggesting that AQP4-dependent bulk flow along the