Brain Extracellular Space: Geometry, Matrix and Physiological Importance

What is ECS and why is it important? rain tissue is essentially composed of two regions: cellular elements (neurons and glial cells), and the gap between the elements, which is known as the extra-cellular space (ECS; Figure 1) (Sykova & Nicholson, 2008). The ECS resembles the water phase of a foam and remains a highly connected domain even though it is convoluted in shape and may form dead-space microdomains (e.g. local expansions or voids) The surprisingly large relative volume of the ECS makes it an important area for neuroscience research. Extracellular space is the immediate external environment of brain cells. This proximity to the cell membrane makes the structure and content of the ECS important for cellular homeostasis and function. The ECS contains a fluid similar in composition to that found in the brain ventricles that maintains an ionic balance for Ca 2+ , Na + , K + and Cl-across the cell membrane. Such an ionic balance establishes the cellular resting potential and permits neuronal action potentials and synaptic transmission. The ECS also provides a communication channel between cells through which chemical signals travel; this is known as volume transmission (Agnati, Fuxe, Nich-olson, & Sykova, 2000). Clinically, the ECS is an important route for the delivery of drugs after they have entered the brain (Wolak & Thorne, 2013). B Figure 1. Schematic of brain cells and ECS. The ECS may have local expansions. Figure 2. Schematic of the extracellular matrix as a mesh-work of long-chain molecules distributed in ECS. Besides an ionic fluid, the ECS accommodates an extra-cellular matrix formed from a meshwork of long-chain polymeric molecules and proteins (Figure 2). These include chondroitin sulfate, heparin sulfate and tenasin that often branch off from a hyaluronic acid backbone (Zim-mermann & Dours-Zimmermann, 2008). Diffusion is the dominant mechanism for transport of substances in ECS and determines both the local and global distribution of many molecules. Both geometry of ECS and the properties of the extra-cellular matrix affect diffusion. The geometry of the ECS hinders free diffusion of molecules in general, while the matrix may increase local viscosity or act more specifically on molecules that undergo steric or electrostatic binding with the matrix.