Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology
Solutes, but not cells, drain from the brain parenchyma along basement membranes of capillaries and arteries: significance for cerebral amyloid angiopathy and neuroimmunology
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DOI：
10.1111/j.1365-2990.2007.00926.x
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发表时间：
2008-04-01
影响因子：
5
通讯作者：
Weller, R. O.
中科院分区：
文献类型：
--
作者：
Carare, R. O.;Bernardes-Silva, M.;Weller, R. O.
间质液和溶质的消除在脑内稳态中起作用，但途径尚不清楚。先前的研究表明，组织间液沿着动脉壁排出。目的：确定毛细血管和动脉壁内将液体和溶质排出大脑的路径。研究方法：将荧光可溶性示踪剂葡聚糖（3 kDa）和卵清蛋白（40 kDa）以及颗粒荧光球（直径为0.02 μ m和1.0 μ m）注射到小鼠纹状体中。从5分钟到7天，通过免疫细胞化学和共聚焦显微镜检查脑。结果如下：可溶性示踪剂最初通过脑实质扩散，然后沿着毛细血管和动脉的基底膜沿着流出脑。一些示踪剂被血管平滑肌细胞和血管周围的巨噬细胞吸收。在心脏骤停后将右旋糖酐注射到小鼠脑中时，没有观察到血管周围引流。荧光球扩大血管壁和周围脑之间的血管周围空间，被血管周围巨噬细胞摄取，但即使在脂多糖或红藻氨酸盐的炎症激发后也不会离开脑。结论：毛细血管和动脉基底膜充当用于排出流体和溶质的“脑的排泄物”;这种排出似乎需要持续的心输出量，因为它在心脏骤停后停止。这种引流途径不允许细胞从脑实质迁移到外周。β淀粉样蛋白沉积在脑淀粉样血管病的基底膜引流途径中，并且可能阻碍阿尔茨海默病中β淀粉样蛋白和间质液从脑中的消除。可溶性抗原，而不是细胞，通过血管周围途径从脑中排出。这种非典型的引流模式可能有助于大脑的部分免疫赦免，并在神经免疫疾病（如多发性硬化症）中发挥作用。
Elimination of interstitial fluid and solutes plays a role in homeostasis in the brain, but the pathways are unclear. Previous work suggests that interstitial fluid drains along the walls of arteries. Aims: to define the pathways within the walls of capillaries and arteries for drainage of fluid and solutes out of the brain. Methods: Fluorescent soluble tracers, dextran (3 kDa) and ovalbumin (40 kDa), and particulate fluospheres (0.02 mu m and 1.0 mu m in diameter) were injected into the corpus striatum of mice. Brains were examined from 5 min to 7 days by immunocytochemistry and confocal microscopy. Results: soluble tracers initially spread diffusely through brain parenchyma and then drain out of the brain along basement membranes of capillaries and arteries. Some tracer is taken up by vascular smooth muscle cells and by perivascular macrophages. No perivascular drainage was observed when dextran was injected into mouse brains following cardiac arrest. Fluospheres expand perivascular spaces between vessel walls and surrounding brain, are ingested by perivascular macrophages but do not appear to leave the brain even following an inflammatory challenge with lipopolysaccharide or kainate. Conclusions: capillary and artery basement membranes act as 'lymphatics of the brain' for drainage of fluid and solutes; such drainage appears to require continued cardiac output as it ceases following cardiac arrest. This drainage pathway does not permit migration of cells from brain parenchyma to the periphery. Amyloid-beta is deposited in basement membrane drainage pathways in cerebral amyloid angiopathy, and may impede elimination of amyloid-beta and interstitial fluid from the brain in Alzheimer's disease. Soluble antigens, but not cells, drain from the brain by perivascular pathways. This atypical pattern of drainage may contribute to partial immune privilege of the brain and play a role in neuroimmunological diseases such as multiple sclerosis.