Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system.
Clearance from the mouse brain by convection of interstitial fluid towards the ventricular system.
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DOI：
10.1186/s12987-015-0019-5
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发表时间：
2015-10-05
影响因子：
7.3
通讯作者：
Bakker EN
中科院分区：
文献类型：
--
作者：
Bedussi B;van Lier MG;Bartstra JW;de Vos J;Siebes M;VanBavel E;Bakker EN
在脑实质中没有真正的淋巴系统的情况下，已经提出了替代的清除多余液体和废物的途径。提示清除机制涉及脑间质和脑脊液的作用。然而，提出的流动方向、所涉及的解剖结构和驱动力是有争议的。为了追踪间质和脑脊液在脑中的分布，并确定所涉及的解剖结构，我们将不同大小的荧光示踪剂混合注入小鼠大脑的枕大池或纹状体。随后，我们对大脑水平切片进行了共聚焦荧光成像，并对小鼠的大脑和血管系统进行了3D重建。我们观察到示踪剂从脑实质到脑室系统的分布模式，从那里示踪剂与脑脊液混合，到达蛛网膜下腔，并通过筛板和鼻子离开大脑。在枕大池和纹状体注射后，示踪剂也进入动脉周围的血管旁间隙，但这似乎是次要的。这些数据表明大量间质液体从纹状体流向邻近的侧脑室。示踪剂可以从两侧进入动脉血管旁间隙，既可以通过实质的大量流动，也可以通过蛛网膜下腔内脑脊液的混合。这一转运途径的紊乱可能会影响淀粉样蛋白β和其他废物的排出，这可能与阿尔茨海默病的病理生理学有关。本文的在线版本(doi：10.1186/s12987-0150019-5)包含补充材料，授权用户可以使用。
In the absence of a true lymphatic system in the brain parenchyma, alternative clearance pathways for excess fluid and waste products have been proposed. Suggested mechanisms for clearance implicate a role for brain interstitial and cerebrospinal fluids. However, the proposed direction of flow, the anatomical structures involved, and the driving forces are controversial. To trace the distribution of interstitial and cerebrospinal fluid in the brain, and to identify the anatomical structures involved, we infused a mix of fluorescent tracers with different sizes into the cisterna magna or striatum of mouse brains. We subsequently performed confocal fluorescence imaging of horizontal brain sections and made 3D reconstructions of the mouse brain and vasculature. We observed a distribution pattern of tracers from the parenchyma to the ventricular system, from where tracers mixed with the cerebrospinal fluid, reached the subarachnoid space, and left the brain via the cribriform plate and the nose. Tracers also entered paravascular spaces around arteries both after injection in the cisterna magna and striatum, but this appeared to be of minor importance. These data suggest a bulk flow of interstitial fluid from the striatum towards the adjacent lateral ventricle. Tracers may enter arterial paravascular spaces from two sides, both through bulk flow from the parenchyma and through mixing of CSF in the subarachnoid space. Disturbances in this transport pathway could influence the drainage of amyloid β and other waste products, which may be relevant for the pathophysiology of Alzheimer’s disease. The online version of this article (doi:10.1186/s12987-015-0019-5) contains supplementary material, which is available to authorized users.