%0 Journal Article %1 Nich_2000_129 %A Nicholson, C. %A Chen, K. C. %A Hrabetov�, S. %A Tao, L. %D 2000 %J Prog. Brain. Res. %K 11098654 Animals, Biological, Brain Chemical, Chemistry, Diffusion, Extracellular Gov't, Models, P.H.S., Research Space, Support, Synaptic Transmission, U.S. %P 129--154 %T Diffusion of molecules in brain extracellular space: theory and experiment. %U http://dx.doi.org/10.1016/S0079-6123(00)25007-3 %V 125 %X 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.

@article{Nich_2000_129, abstract = {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.}, added-at = {2009-06-03T11:20:58.000+0200}, author = {Nicholson, C. and Chen, K. C. and Hrabetov�, S. and Tao, L.}, biburl = {https://www.bibsonomy.org/bibtex/2bb7c78b5c5c8a4542f5aa34462062814/hake}, description = {The whole bibliography file I use.}, file = {Nich_2000_129.pdf:Nich_2000_129.pdf:PDF}, interhash = {f479b8e96edf173bae3945cb48502df8}, intrahash = {bb7c78b5c5c8a4542f5aa34462062814}, journal = {Prog. Brain. Res.}, key = 178, keywords = {11098654 Animals, Biological, Brain Chemical, Chemistry, Diffusion, Extracellular Gov't, Models, P.H.S., Research Space, Support, Synaptic Transmission, U.S.}, pages = {129--154}, pmid = {11098654}, timestamp = {2009-06-03T11:21:24.000+0200}, title = {Diffusion of molecules in brain extracellular space: theory and experiment.}, url = {http://dx.doi.org/10.1016/S0079-6123(00)25007-3}, volume = 125, year = 2000 }