EXTRACELLULAR-SPACE STRUCTURE REVEALED BY DIFFUSION ANALYSIS

The structure of brain extracellular space resembles foam. Diffusing m olecules execute random movements that cause their collision with memb ranes and affect their concentration distribution. By measuring this d istribution, the volume fraction (alpha) and the tortuosity (lambda) c an be estimated. The volume fraction indicates the relative amount of extracellular space and tortuosity is a measure of hindrance of cellul ar obstructions. Diffusion measurements with molecules <500 M-r show t hat alpha approximate to 0.2 and lambda approximate to 1.6, although s ome 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 thr ough the extracellular space. During stimulation, and in pathophysiolo gical states, alpha and lambda change, for example in severe ischemia alpha = 0.04 and lambda = 2.2. These data support the feasibility of e xtrasynaptic or volume transmission in the extracellular space.