Glymphatic system

The glymphatic system (or glymphatic clearance pathway, or paravascular system) is a system for waste clearance in the central nervous system (CNS) of vertebrates. According to this model, cerebrospinal fluid (CSF) flows into the paravascular space around cerebral arteries, combining with interstitial fluid (ISF) and parenchymal solutes, and exiting down venous paravascular spaces.^[1] The pathway consists of a para-arterial influx route for CSF to enter the brain parenchyma, coupled to a clearance mechanism for the removal of interstitial fluid (ISF) and extracellular solutes from the interstitial compartments of the brain and spinal cord. Exchange of solutes between CSF and ISF is driven primarily by arterial pulsation^[2] and regulated during sleep by the expansion and contraction of brain extracellular space. Clearance of soluble proteins, waste products, and excess extracellular fluid is accomplished through convective bulk flow of ISF, facilitated by astrocytic aquaporin 4 (AQP4) water channels.^[3]

The name "glymphatic system" was coined by the Danish neuroscientist Maiken Nedergaard in recognition of its dependence upon glial cells and the similarity of its functions to those of the peripheral lymphatic system.^[4]

Glymphatic flow was initially believed to be the complete answer to the long-standing question of how the sensitive neural tissue of the CNS functions in the perceived absence of a lymphatic drainage pathway for extracellular proteins, excess fluid, and metabolic waste products. However, two subsequent articles by Louveau et al. from the University of Virginia School of Medicine and Aspelund et al. from the University of Helsinki reported independently that the dural sinuses and meningeal arteries are lined with conventional lymphatic vessels, and that this long-elusive vasculature forms a connecting pathway to the glymphatic system.^[5][6]