Abstract
The paravascular pathway, also known as the “glymphatic” pathway, is a recently described system for waste clearance in the brain. According to this model, cerebrospinal fluid (CSF) enters the paravascular spaces surrounding penetrating arteries of the brain, mixes with interstitial fluid (ISF) and solutes in the parenchyma, and exits along paravascular spaces of draining veins. Studies have shown that metabolic waste products and solutes, including proteins involved in the pathogenesis of neurodegenerative diseases such as amyloid-beta, may be cleared by this pathway. Consequently, a growing body of research has begun to explore the association between glymphatic dysfunction and various disease states. However, significant controversy exists in the literature regarding both the direction of waste clearance as well as the anatomical space in which the waste-fluid mixture is contained. Some studies have found no evidence of interstitial solute clearance along the paravascular space of veins. Rather, they demonstrate a perivascular pathway in which waste is cleared from the brain along an anatomically distinct perivascular space in a direction opposite to that of paravascular flow. Although possible explanations have been offered, none have been able to fully reconcile the discrepancies in the literature, and many questions remain. Given the therapeutic potential that a comprehensive understanding of brain waste clearance pathways might offer, further research and clarification is highly warranted.
Highlights
In peripheral tissues, the lymphatic system functions to clear proteins solutes and metabolic wastes from the interstitial spaces between cells (Ellis, 2006)
It was generally understood that waste substances in the central nervous system (CNS) were cleared to cerebrospinal fluid (CSF) by convective bulk flow of interstitial fluid (ISF) coursing diffusely through brain parenchyma (Cserr et al, 1981; Abbott, 2004; Sykova and Nicholson, 2008), draining into peripheral lymphatics of the neck to reach systemic circulation (Bradbury et al, 1981; Bradbury and Westrop, 1983)
By tracking the movement of small fluorescent tracers, they showed that CSF enters the brain parenchyma along para-arterial spaces, mixes with ISF and solutes, and follows para-venous spaces to be removed from the brain
Summary
The lymphatic system functions to clear proteins solutes and metabolic wastes from the interstitial spaces between cells (Ellis, 2006). By tracking the movement of small fluorescent tracers, they showed that CSF enters the brain parenchyma along para-arterial spaces, mixes with ISF and solutes, and follows para-venous spaces to be removed from the brain. This paravascular pathway was termed the ‘‘glymphatic’’ system due to its dependence on glial cells and functional similarity to the peripheral lymphatic system (Iliff et al, 2012). Disagreement still exists in the literature regarding the structures involved in interstitial waste clearance and the direction of fluid flow This brief review article will examine the anatomy, function and clinical significance of the paravascular pathway, as well as the controversy associated with it. An examination of what is currently known and what remains to be clarified may provide inspiration for future research on this clinically important topic
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
