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 (alpha) and the tortuosity (lambda) 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 M-r show that alpha approximate to 0.2 and lambda approximate to 1.6, although some brain regions are anisotropic. Molecules greater than or equal to 3000 M-r show more hindrance, but molecules of 70 000 M-r can move through the extracellular space.
During stimulation, and in pathophysiological states, alpha and lambda change, for example in severe ischemia alpha = 0.04 and lambda = 2.2. These data support the feasibility of extrasynaptic or volume transmission in the extracellular space.