Document Detail


Random-walk model of diffusion in three dimensions in brain extracellular space: comparison with microfiberoptic photobleaching measurements.
MedLine Citation:
PMID:  18469079     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Diffusion through the extracellular space (ECS) in brain is important in drug delivery, intercellular communication, and extracellular ionic buffering. The ECS comprises approximately 20% of brain parenchymal volume and contains cell-cell gaps approximately 50 nm. We developed a random-walk model to simulate macromolecule diffusion in brain ECS in three dimensions using realistic ECS dimensions. Model inputs included ECS volume fraction (alpha), cell size, cell-cell gap geometry, intercellular lake (expanded regions of brain ECS) dimensions, and molecular size of the diffusing solute. Model output was relative solute diffusion in water versus brain ECS (D(o)/D). Experimental D(o)/D for comparison with model predictions was measured using a microfiberoptic fluorescence photobleaching method involving stereotaxic insertion of a micron-size optical fiber into mouse brain. D(o)/D for the small solute calcein in different regions of brain was in the range 3.0-4.1, and increased with brain cell swelling after water intoxication. D(o)/D also increased with increasing size of the diffusing solute, particularly in deep brain nuclei. Simulations of measured D(o)/D using realistic alpha, cell size and cell-cell gap required the presence of intercellular lakes at multicell contact points, and the contact length of cell-cell gaps to be least 50-fold smaller than cell size. The model accurately predicted D(o)/D for different solute sizes. Also, the modeling showed unanticipated effects on D(o)/D of changing ECS and cell dimensions that implicated solute trapping by lakes. Our model establishes the geometric constraints to account quantitatively for the relatively modest slowing of solute and macromolecule diffusion in brain ECS.
Authors:
Songwan Jin; Zsolt Zador; A S Verkman
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-09
Journal Detail:
Title:  Biophysical journal     Volume:  95     ISSN:  1542-0086     ISO Abbreviation:  Biophys. J.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-07-28     Completed Date:  2008-08-28     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1785-94     Citation Subset:  IM    
Affiliation:
Departments of Medicine and Physiology, University of California, San Francisco, California, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Biopolymers / chemistry*
Brain Chemistry*
Computer Simulation
Diffusion
Fiber Optic Technology
Fluorescence Recovery After Photobleaching / methods*
Mice
Models, Biological*
Optical Fibers
Grant Support
ID/Acronym/Agency:
DK35124/DK/NIDDK NIH HHS; DK72517/DK/NIDDK NIH HHS; EB00415/EB/NIBIB NIH HHS; EY13574/EY/NEI NIH HHS; HL59198/HL/NHLBI NIH HHS; HL73856/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Biopolymers
Comments/Corrections

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