B 1: cross-section through an idealized 2D square brain region bounded by impermeable walls and containing a number of circular cellular profiles. Molecules executing Random walks reveal structure. Even though the ECS is probably reduced in width due to fixation procedure it is still evident that it is not completely uniform in width. The ECS is outlined in red it has a well-connected foam-like structure formed from the interstices of simple convex cell surfaces. Electronmicrograph of small region of rat cortex with dendritic spine and synapse. Knowledge of ECS diffusion properties are valuable in contexts ranging from understanding extrasynaptic volume transmission to the development of paradigms for drug delivery to the brain.īasic concepts of ECS. Overall, these studies improve our conception of ECS structure and the roles of glia and extracellular matrix in modulating the ECS microenvironment. Measurements have also been made during ischemia, in models of Alzheimer's and Parkinson's diseases and in human gliomas. Diffusion properties have been characterized in several interventions, including brain stimulation, osmotic challenge and knockout of extracellular matrix components. These parameters change during development and aging. free diffusion coefficient of TMA is reduced by 2.6), although there are regional variations. Extensive experimental studies with the RTI method employing the cation tetramethylammonium (TMA) in normal brain tissue show that the volume fraction of the ECS typically is about 20% and the tortuosity about 1.6 (i.e. Theoretical models and simulations of the ECS have explored the influence of ECS geometry, effects of dead-space microdomains, extracellular matrix and interaction of macromolecules with ECS channels. Presently, the real-time iontophoresis (RTI) method is employed for small ions and the integrative optical imaging (IOI) method for fluorescent macromolecules, including dextrans or proteins. Early diffusion measurements used radiolabeled sucrose and other tracers. Deviations from the equation reveal loss of molecules across the blood-brain barrier, through cellular uptake, binding or other mechanisms. Diffusion in the extracellular space (ECS) of the brain is constrained by the volume fraction and the tortuosity and a modified diffusion equation represents the transport behavior of many molecules in the brain.
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