Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer's disease.
Periarteriolar spaces modulate cerebrospinal fluid transport into brain and demonstrate altered morphology in aging and Alzheimer's disease.
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DOI：
10.1038/s41467-022-31257-9
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发表时间：
2022-07-06
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
血管周围间隙(PVS)排出脑废物代谢物，但其具体的流动路径仍有争议。据报道，脑膜软膜形成了限制血管周围血流的最外边界。然而，我们发现PIA是穿孔的，并且允许PVS流体流动。此外，我们证明了PIA是由沿着软脑膜动脉以不同模式结合的血管层和脑层组成的，通常合并在穿透小动脉周围。不同的软膜结构形成不同的筛状结构，不同地影响脑脊液(CSF)沿PVS的传输。硬膜覆盖程度与巨噬细胞密度和脑脊液示踪剂吞噬功能有关。活体成像证实脑脊液示踪剂经鼻流入，提示pia在脑脊液滤过中起作用，但不是血流限制。此外，随着年龄的增长，软膜层萎缩。老年小鼠也表现出幼年动物没有观察到的软膜剥脱区域，但在阿尔茨海默病小鼠模型中，Pia出人意料地肥大。此外，软膜厚度与老年小鼠脑脊液流量的改善和PVS中β-淀粉样蛋白沉积的减少有关。我们发现，小鼠PVS的形态是多种多样的，Pia的结构和功能表明，在衰老和疾病中，Pia在调节脑脊液运输和淀粉样蛋白清除方面具有以前未知的作用。大脑中血管周围空间的精确边界和流动隔间尚不完全清楚。作者发现，PIA是穿孔的，允许脑脊液流动，形成三种类型的血管周围空间，随着年龄的增加而重塑，其中一种异常类型出现在阿尔茨海默病中，与β-淀粉样蛋白负荷和不同的巨噬细胞摄取相关。
Perivascular spaces (PVS) drain brain waste metabolites, but their specific flow paths are debated. Meningeal pia mater reportedly forms the outermost boundary that confines flow around blood vessels. Yet, we show that pia is perforated and permissive to PVS fluid flow. Furthermore, we demonstrate that pia is comprised of vascular and cerebral layers that coalesce in variable patterns along leptomeningeal arteries, often merging around penetrating arterioles. Heterogeneous pial architectures form variable sieve-like structures that differentially influence cerebrospinal fluid (CSF) transport along PVS. The degree of pial coverage correlates with macrophage density and phagocytosis of CSF tracer. In vivo imaging confirms transpial influx of CSF tracer, suggesting a role of pia in CSF filtration, but not flow restriction. Additionally, pial layers atrophy with age. Old mice also exhibit areas of pial denudation that are not observed in young animals, but pia is unexpectedly hypertrophied in a mouse model of Alzheimer’s disease. Moreover, pial thickness correlates with improved CSF flow and reduced β-amyloid deposits in PVS of old mice. We show that PVS morphology in mice is variable and that the structure and function of pia suggests a previously unrecognized role in regulating CSF transport and amyloid clearance in aging and disease. The precise boundaries and flow compartments of perivascular spaces in the brain are incompletely understood. Here the authors show that pia is perforated and permissive to CSF flow, forming three types of perivascular spaces that remodel with age, with an abnormal type arising in Alzheimer’s disease and correlating with β-amyloid burden and differential macrophage uptake.
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影响因子：
12.7
作者：
Lie, AA;Schröder, R;Elger, CE
通讯作者：
Elger, CE
简单，可扩展的蛋白质组学成像，用于完整系统的高维分析。
影响因子：
64.5
作者：
Murray E;Cho JH;Goodwin D;Ku T;Swaney J;Kim SY;Choi H;Park YG;Park JY;Hubbert A;McCue M;Vassallo S;Bakh N;Frosch MP;Wedeen VJ;Seung HS;Chung K
通讯作者：
Chung K
影响因子：
4
作者：
Bakker EN;Bacskai BJ;Arbel-Ornath M;Aldea R;Bedussi B;Morris AW;Weller RO;Carare RO
通讯作者：
Carare RO
影响因子：
17.1
作者：
Iliff JJ;Wang M;Liao Y;Plogg BA;Peng W;Gundersen GA;Benveniste H;Vates GE;Deane R;Goldman SA;Nagelhus EA;Nedergaard M
通讯作者：
Nedergaard M
影响因子：
5.5
作者：
Pizzo, Michelle E.;Wolak, Daniel J.;Thorne, Robert G.
通讯作者：
Thorne, Robert G.