The Glymphatic System: A Novel Therapeutic Target for Stroke Treatment

• Published in: Frontiers in aging neuroscience Vol. 13; p. 689098
• Main Authors: Lv, Tao, Zhao, Bing, Hu, Qin, Zhang, Xiaohua
• Format: Journal Article
• Language: English
• Published: Lausanne Frontiers Research Foundation 08.07.2021; Frontiers Media S.A
• Subjects: Alzheimer's disease; Apoptosis; AQP4; Aquaporin 4; Aquaporins; Astrocytes; Blood-brain barrier; Brain research; Cerebrospinal fluid; Cytokines; Edema; Epilepsy; glymphatic system; Headache; Hemorrhage; Hydrocephalus; Immune clearance; Inflammation; Lymphatic system; meningeal lymphatic system; Metabolism; Metabolites; Migraine; Nervous system; Neurodegenerative diseases; Neurological diseases; Neuroscience; Neurotoxicity; Pathophysiology; Physiology; Risk assessment; Solutes; Stroke; Therapeutic targets; Traumatic brain injury; Veins & arteries
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2021.689098

The glymphatic system (GS) is a novel defined brain-wide perivascular transit network between cerebrospinal fluid (CSF) and interstitial solutes that facilitates the clearance of brain metabolic wastes. The complicated network of the GS consists of the periarterial CSF influx pathway, astrocytes-mediated convective transport of fluid and solutes supported by AQP4 water channels, and perivenous efflux pathway. Recent researches indicate that the GS dysfunction is associated with various neurological disorders, including traumatic brain injury, hydrocephalus, epilepsy, migraine, and Alzheimer’s disease (AD). Meanwhile, the GS also plays a pivotal role in the pathophysiological process of stroke, including brain edema, blood–brain barrier (BBB) disruption, immune cell infiltration, neuroinflammation, and neuronal apoptosis. In this review, we illustrated the key anatomical structures of the GS, the relationship between the GS and the meningeal lymphatic system, the interaction between the GS and the BBB, and the crosstalk between astrocytes and other GS cellular components. In addition, we contributed to the current knowledge about the role of the GS in the pathology of stroke and the role of AQP4 in stroke. We further discussed the potential use of the GS in early risk assessment, diagnostics, prognostics, and therapeutics of stroke.