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The brain consists of four fluid compartments: cerebrospinal fluid (CSF), interstitial fluid, intracellular fluid, and the blood vasculature ( Fig. Finally, we discuss our recent findings indicating that this system might also serve to distribute non-waste compounds such as lipids and glucose within the brain.

This review addresses recent findings that shed light on this paradox and discusses these findings within the broader context of what is known about waste elimination from the CNS. Although the brain and spinal cord are characterized by a disproportionally high metabolic rate, and synaptic transmission is exquisitely sensitive to changes in their environment, the central nervous system (CNS) completely lacks conventional lymphatic vessels. The lymphatic network extends throughout all parts of the peripheral tissues and the density of lymph vessels correlates with the rate of tissue metabolism. In the peripheral tissues soluble material, proteins and fluid from the interstitial space are returned to the general circulation by the lymphatic system. We will also discuss recent studies indicating that glymphatic function is suppressed in various diseases and that failure of glymphatic function in turn might contribute to pathology in neurodegenerative disorders, traumatic brain injury and stroke.Ĭlearance of excess fluid and interstitial solutes is critical for tissue homeostasis.

Since the concept of the glymphatic system is relatively new, we will here review its basic structural elements, organization, regulation, and functions. The biological need for sleep across all species may therefore reflect that the brain must enter a state of activity that enables elimination of potentially neurotoxic waste products, including β-amyloid. Intriguingly, the glymphatic system function mainly during sleep and is largely disengaged during wakefulness. Besides waste elimination, the glymphatic system may also function to help distribute non-waste compounds, such as glucose, lipids, amino acids, and neurotransmitters related to volume transmission, in the brain. The glymphatic system is a recently discovered macroscopic waste clearance system that utilizes a unique system of perivascular channels, formed by astroglial cells, to promote efficient elimination of soluble proteins and metabolites from the central nervous system.

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