Diffusion of molecules in brain extracellular space: theory and experiment.
Volume transmission depends on the migration of informational substances through brain extracellular space (ECS) and almost always involves diffusion; basic concepts of diffusion are outlined from both the microscopic viewpoint based on random walks and the macroscopic viewpoint based on the solution of equations embodying Fick's Laws. In a complex medium like the brain, diffusing molecules are constrained by the local volume fraction of the ECS and tortuosity, a measure of the hindrance imposed by cellular obstacles. Molecules can also experience varying degrees of uptake or clearance. Bulk flow and the extracellular matrix may also play a role. Examples of recent work on diffusion of tetramethylammonium (molecular weight, 74) in brain slices, using iontophoretic application and ion-selective microelectrodes, are reviewed. In slices, the volume fraction is about 20% and tortuosity about 1.6, both similar to values found in the intact brain. Using integrative optical imaging, results obtained with dextrans and albumins up to a molecular weight of 70,000 are summarized, for such large molecules the tortuosity is about 2.3. Experiments using synthetic long-chain PHPMA polymers up to 1,000,000 molecular weight show that these molecules also diffuse in the ECS but with a tortuosity of about 1.6. Studies with osmotic challenge show that volume fraction and tortuosity do not vary together as expected when the size of the ECS changes; a model is presented that explains the osmotic-challenge on the basis of changes in cell shape. Finally, new analytical insights are provided into the complex movement of potassium in the brain.
Nicholson
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Department of Physiology and Neuroscience, New York University School of Medicine, NY 10016, USA. cn7@is.nyu.edu
Chen
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KC
Hrabĕtová
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Tao
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D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D004058:Diffusion; D005110:Extracellular Space / Q000737:chemistry / Q000378:metabolism*; D008954:Models, Biological; D008956:Models, Chemical; D009435:Synaptic Transmission / Q000502:physiology*