The Glymphatic Pathway: Waste Removal from the CNS via Cerebrospinal Fluid Transport

Abstract

The overall premise of this review is that cerebrospinal fluid (CSF) is transported within a dedicated peri-vascular network facilitating metabolic waste clearance from the central nervous system while we sleep. The anatomical profile of the network is complex and has been defined as a peri-arterial CSF influx pathway and peri-venous clearance routes, which are functionally coupled by interstitial bulk flow supported by astrocytic aquaporin 4 water channels. The role of the newly discovered system in the brain is equivalent to the lymphatic system present in other body organs and has been termed the “glymphatic pathway” or “(g)lymphatics” because of its dependence on glial cells. We will discuss and review the general anatomy and physiology of CSF from the perspective of the glymphatic pathway, a discovery which has greatly improved our understanding of key factors that control removal of metabolic waste products from the central nervous system in health and disease and identifies an additional purpose for sleep. A brief historical and factual description of CSF production and transport will precede the ensuing discussion of the glymphatic system along with a discussion of its clinical implications.

A longitudinal study of polysomnographic variables in patients with mild cognitive impairment converting to Alzheimer's disease

“…Thus, recurring sleep loss and/or impaired NREM sleep organization could determine long-term cognitive consequences, by impacting the pathways proposed to play a role in degenerative processes taking place in AD (Benveniste, Lee, & Volkow, 2017;Jessen, Munk, Lundgaard, & Nedergaard, 2015;Spira et al, 2016), through build-up and accumulation of hazardous wastes and may therefore extend the neurocognitive correlates of sleep to a longitudinal basis. On one hand, chronically increased synaptic load and strength and β-amyloid levels may be considered as a potential initiating and perpetuating factor in the pathological cascade.…”

Influence of spatial structure on protein damage susceptibility – A bioinformatics approach

“…This allows them to get rid of damaged proteins by asymmetric division or apoptosis. Multicellular organisms, on the other hand, do the same, but the damaged proteins remain in the intercellular spaces or have to be expensively transported away (immune cells, [43,44]). We hypothetize that the outer cell layers (e.g.…”

Significance of Understanding Function of Glymphatic System to Manage Practical Clinical Problems of the Elderly

“…Recent investigations revealed that CSF is exchanged rapidly with interstitial fluid by three highly organized pathways: 1. the para-arterial CSF route, 2. the paravenous interstitial clearance route and 3. The intracellular, transparenchymal-glial (astrocytic) route that connects the two mentioned paravascular routes [1,2,4,6]. We try to illustrate this system in Figure 2.…”

“…The glymphatic system is contemporarily one of the most studied functional systems of the human body [1][2][3][4][5][6]. Much work has also already been devoted to the significance of impaired function of the glymphatic system in the development of dementia and other neurodegenerative diseases [7,8,9].…”