A novel conceptual framework for the functionality of the glymphatic system

The glymphatic system is responsible for the clearance of the potentially harmful metabolic waste of the central nervous system. The prevalent theory is that the cerebrospinal fluid (CSF) circulates in the perivascular space (PVS) and through the astrocytes' aquaporin-4 channels (AQ-4), and it is then drained by the lymphatic vessels after mixing with interstitial fluid (ISF). However, there is little evidence supporting this hypothesis. A deeper understanding of the physiology of the glymphatic system could transform the way we understand neuropathology and our approach to treating neurological and neuropsychiatric disorders. In this review, we introduce a new conceptual framework for the functionality of the glymphatic system, offering new directions for future research. We propose that CSF and ISF exchange flow depends on arterial pulsation, respiration, posture, and sleep. PVS changes due to disrupted cerebral autoregulation, alternations of intrathoracic pressure, venous flow, and body position can also influence the glymphatic flow. The role of respiration remains controversial due to the variety of parameters that interfere with glymphatic functionality. Slow-wave sleep is important for glymphatic clearance due to neuronal electromagnetic synchronization and expansion of the interstitial space. Therefore, sleep and vascular disorders, as well as aging, may hinder glymphatic flow and induce a noxious milieu of susceptibility to neurodegenerative disorders because of metabolic waste accumulation. We lastly introduce a new idea postulating that electromagnetic induction may constitute one of the propelling forces for the convectional current and mixing of CSF and ISF.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:129

Enthalten in:

Journal of neurophysiology - 129(2023), 5 vom: 01. Mai, Seite 1228-1236

Sprache:

Englisch

Beteiligte Personen:

Astara, Kyriaki [VerfasserIn]
Pournara, Christina [VerfasserIn]
de Natale, Edoardo Rosario [VerfasserIn]
Wilson, Heather [VerfasserIn]
Vavougios, George D [VerfasserIn]
Lappas, Andreas S [VerfasserIn]
Politis, Marios [VerfasserIn]
Christodoulou, Nikos G [VerfasserIn]

Links:

Volltext

Themen:

Cerebral autoregulation
Glymphatic
Journal Article
Respiration
Review
Sleep

Anmerkungen:

Date Completed 19.05.2023

Date Revised 14.06.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1152/jn.00360.2022

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM355778378