Extracellular space structure revealed by diffusion analysis

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Abstract

The structure of brain extracellular space resembles foam. Diffusing molecules execute random movements that cause their collision with membranes and affect their concentration distribution. By measuring this distribution, the volume fraction (α) and the tortuosity (λ) can be estimated. The volume fraction indicates the relative amount of extracellular space and tortuosity is a measure of hindrance of cellular obstructions. Diffusion measurements with molecules <500 Mr show that α 0.2 and λ 1.6, although some brain regions are anisotropic. Molecules ≥3000 Mr show more hindrance, but molecules of 70 000 Mr can move through the extracellular space. During stimulation, and in pathophysiological states, α and λ change, for example in severe ischemia α = 0.04 and λ = 2.2.  These data support the feasibility of extrasynaptic or volume transmission in the extracellular space.

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