期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 38, 期 4, 页码 669-686出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X17749689
关键词
Basement membranes; cerebrospinal fluid; fluid flow; laminin; perivascular pathways
资金
- German Research Foundation [SFB 1009 A02, TR128 B03, EXC 1003]
- EU FP7 European Stroke Network [202213]
- SVDs@target consortium - European Union [666881]
- University of Wisconsin-Madison School of Pharmacy
- Clinical and Translational Science Award program administered through the NIH National Center for Advancing Translational Sciences [NIH UL1TR000427, KL2TR00428]
- National Science Foundation Graduate Research Fellowship [DGE-1256259]
Perivascular compartments surrounding central nervous system (CNS) vessels have been proposed to serve key roles in facilitating cerebrospinal fluid flow into the brain, CNS waste transfer, and immune cell trafficking. Traditionally, these compartments were identified by electron microscopy with limited molecular characterization. Using cellular markers and knowledge on cellular sources of basement membrane laminins, we here describe molecularly distinct compartments surrounding different vessel types and provide a comprehensive characterization of the arachnoid and pial compartments and their connection to CNS vessels and perivascular pathways. We show that differential expression of plectin, E-cadherin and laminins alpha 1, alpha 2, and alpha 5 distinguishes pial and arachnoid layers at the brain surface, while endothelial and smooth muscle laminins alpha 4 and alpha 5 and smooth muscle actin differentiate between arterioles and venules. Tracer studies reveal that interconnected perivascular compartments exist from arterioles through to veins, potentially providing a route for fluid flow as well as the transport of large and small molecules.
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