The extracellular space (ECS) may be imagined as a system of interconnected channels demarcated by cellular membranes (Figure 10.1) and filled with an ionic solution, primarily NaCl, along with macromolecules of the extracellular matrix, negatively-charged proteoglycans and glycosaminoglycans (Margolis and Margolis 1993; Ruoslahti 1996; Novak and Kaye 2000). The ECS mediates intercellular communication (Nicholson 1979) and the transport of nutrients and metabolites (Syková et al. 2000), and it forms a reservoir of ions that establishes the resting potentials of cells and mediate fluxes across the membranes. It also may serve to deliver therapeutic substances to cells (Ulbrich et al. 1997; Saltzman 2001). All these processes are primarily mediated by diffusion. The ECS diffusive properties are thus critical for neurotransmission over short and long distances (the latter being called volume transmission, Fuxe and Agnati 1991; Agnati et al. 2000), neurotrophic effects, general electrical activity, basic cellular homeostasis, and drug delivery. This chapter will introduce the brain ECS, describe techniques and preparations most commonly used to measure diffusion properties together with relevant theory and software for data analysis, review selected findings, demonstrate the utility of mathematical modeling and computer simulations, and outline some future directions for research.
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