Document Detail

Diffusion Properties of Molecules at the Blood-Brain Interface: Potential Contributions of Astrocyte Endfeet to Diffusion Barrier Functions.
MedLine Citation:
PMID:  22776675     Owner:  NLM     Status:  Publisher    
Molecular diffusion in the extracellular space (ECS) plays a key role in determining tissue physiology and pharmacology. The blood-brain barrier regulates the exchange of substances between the brain and the blood, but the diffusion properties of molecules at this blood-brain interface, particularly around the astrocyte endfeet, are poorly characterized. In this study, we used 2-photon microscopy and acute brain slices of mouse neocortex and directly assessed the diffusion patterns of fluorescent molecules. By observing the diffusion of unconjugated and 10-kDa dextran-conjugated Alexa Fluor 488 from the ECS of the brain parenchyma to the blood vessels, we find various degrees of diffusion barriers at the endfeet: Some allow the invasion of dye inside the endfoot network while others completely block it. Detailed analyses of the time course for dye clearance support the existence of a tight endfoot network capable of acting as a diffusion barrier. Finally, we show that this diffusion pattern collapses under pathological conditions. These data demonstrate the heterogeneous nature of molecular diffusion dynamics around the endfeet and suggest that these structures can serve as the diffusion barrier. Therefore, astrocyte endfeet may add another layer of regulation to the exchange of molecules between blood vessels and brain parenchyma.
Mutsuo Nuriya; Takanori Shinotsuka; Masato Yasui
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-9
Journal Detail:
Title:  Cerebral cortex (New York, N.Y. : 1991)     Volume:  -     ISSN:  1460-2199     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9110718     Medline TA:  Cereb Cortex     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pharmacology, School of Medicine, Keio University, Shinjuku, Tokyo 160-8582, Japan.
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