[Measurement of brain extracellular space and its physiological and pathophysiological significance]

The extracellular space (ECS) of brain is defined as an irregular channel which is located in the interstitial tissue outside the plasma membranes of neurons, and occupied by interstitial fluid (ISF). Diffusion in ECS is described by a modified diffusion equation from which several parameters can be calculated, such as the diffusion coefficient (D), the tortuosity (Lambda), the volume fraction (alpha) and the clearance of molecules. Radiolabeled tracers were used for early diffusion measurements. Presently, the real-time iontophoresis (RTI) method is employed for small ions, whereas the integrative optical imaging (IOI) and the magnetic resonance diffusion weighted imaging (DWI) are developed for macromolecules tracers. Extensive experimental studies with such methods show that in normal brain tissue, the volume fraction of ECS typically is about 20% and the tortuosity is 1.6, although there are regional variations. These parameters change with the brain development and in various pathophysiological states. Knowledge of ECS diffusion properties help us to understand extrasynaptic volume transmission to the development of paradigms for drug delivery in brain.