Abstract
There is increasing evidence that long-term changes in the physical and chemical parameters of the extracellular space (ECS) accompany many physiological and pathological states. The acute or relatively fast changes in the size of the intercellular channels are apparently a consequence of cellular (particularly glial) swelling.
Abrupt ECS volume decrease may cause cellular or molecular crowding, which can lead to an acute increase in tortuosity. Long-term changes in diffusion would require changes in ECS composition, either permanent changes in the size of the intercellular channels, changes in extracellular matrix molecules, or changes in the number and thickness of cellular processes.
Available data suggest that in some pathophysiological states α and λ behave as independent variables. A persistent increase in λ (without a decrease in ECS volume) is always found during astrogliosis and in myelinated tissue, suggesting that glial cells can form diffusion barriers, make the nervous tissue less permissive and play an important role in signal transmission, tissue regeneration, and pathological states.
The extracellular matrix apparently also contributes to diffusion barriers and to diffusional anisotropy, particularly since its loss, for example, during aging, correlates with a tortuosity decrease and a loss of anisotropy.