Diffusion Properties of Molecules at the BloodBrain Interface: Potential Contributions of Astrocyte Endfeet to Diffusion Barrier Functions

作者：Nuriya Mutsuo^*; Shinotsuka Takanori; Yasui Masato

来源：Cerebral Cortex, 2013, 23(9): 2118-2126.

DOI：10.1093/cercor/bhs198

• astrocyte
• diffusion
• endfoot
• extracellular space
• 2-photon microscopy

Molecular diffusion in the extracellular space (ECS) plays a key role in determining tissue physiology and pharmacology. The bloodbrain barrier regulates the exchange of substances between the brain and the blood, but the diffusion properties of molecules at this bloodbrain 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.

• 出版日期2013-9