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The role of astrocytes in the glymphatic network: a narrative review

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Abstract

To date, treatment of Central Nervous System (CNS) pathology has largely focused on neuronal structure and function. Yet, revived attention towards fluid circulation within the CNS has exposed the need to further explore the role of glial cells in maintaining homeostasis within neural networks. In the past decade, discovery of the neural glymphatic network has revolutionized traditional understanding of fluid dynamics within the CNS. Advancements in neuroimaging have revealed alternative pathways of cerebrospinal fluid (CSF) generation and efflux. Here, we discuss emerging perspectives on the role of astrocytes in CSF hydrodynamics, with particular focus on the contribution of aquaporin-4 channels to the glymphatic network. Astrocytic structural features and expression patterns are detailed in relation to their function in maintaining integrity of the Blood Brain Barrier (BBB) as part of the neurovascular unit (NVU). This narrative also highlights the potential role of glial dysfunction in pathogenesis of neurodegenerative disease, hydrocephalus, intracranial hemorrhage, ischemic stroke, and traumatic brain injury. The purpose of this literature summary is to provide an update on the changing landscape of scientific theory surrounding production, flow, and absorption of cerebrospinal fluid. The overarching aim of this narrative review is to advance the conception of basic, translational, and clinical research endeavors investigating glia as therapeutic targets for neurological disease.

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Funding

This study was supported by funding from the US FDA National Center for Toxicological Research.

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Authors and Affiliations

  1. Division of Neurotoxicology, HFT-132, National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR, 72079, USA

    Sumit Sarkar

  2. Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Nikita Das & Ravi Dhamija

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  1. Nikita Das
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  2. Ravi Dhamija
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Nikita Das (ND) is the lead author who has substantially contributed to writing the manuscript. Ravi Dhamija (RD) has written and helped obtaining literature search and reviewing the manuscript. Sumit Sarkar (SS) is the corresponding author and primary input on experiment design, performed animal sacrifice, tissue processing and immunolabeling of histological sections, data collection and interpretation of photomicrographs and editing of manuscript.

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Correspondence to Sumit Sarkar.

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This review study did not involve human subjects and was performed in accordance with the latest amendments of the 1964 Declaration of Helsinki.

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Das, N., Dhamija, R. & Sarkar, S. The role of astrocytes in the glymphatic network: a narrative review. Metab Brain Dis 39, 453–465 (2024). https://doi.org/10.1007/s11011-023-01327-y

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