Astrocytes in the regulation of cerebrovascular functions

Abstract

Astrocytes are the most numerous type of neuroglia in the brain and have a predominant influence on the cerebrovascular system; they control perivascular homeostasis, the integrity of the blood–brain barrier, the dialogue with the peripheral immune system, the transfer of metabolites from the blood, and blood vessel contractility in response to neuronal activity. These regulatory processes occur in a specialized interface composed of perivascular astrocyte extensions that almost completely cover the cerebral blood vessels. Scientists have only recently started to study how this interface is formed and how it influences cerebrovascular functions. Here, we review the literature on the astrocytes' role in the regulation of the cerebrovascular system. We cover the anatomy and development of the gliovascular interface, the known gliovascular functions, and molecular factors, the latter's implication in certain pathophysiological situations, and recent cutting‐edge experimental tools developed to examine the astrocytes' role at the vascular interface. Finally, we highlight some open questions in this field of research.

Hypothalamic Microglial Heterogeneity and Signature under High Fat Diet–Induced Inflammation

“…Microglia and astrocytes interact via contact-dependent and secreted factors, such as growth factors, neurotransmitters, cytokines, chemokines, innate-immunity mediators, mitogenic factors, ROS, and metabolic mediators such as glutamate, which can be used for cell metabolism and may also mediate tissue changes [ 90 ]. These glial cells play a crucial role in synapse development and function in the healthy CNS, forming the ‘quad-partite’ synapse [ 91 ], which is essential for neuro-immune communication [ 90 ], critically contributing to brain homeostasis [ 92 ].…”

Local translation in perisynaptic and perivascular astrocytic processes – a means to ensure astrocyte molecular and functional polarity?

“…On average, each astrocyte has 3.5 PvAPs (with a range from 1 to 7), which originate from one or more ramifications and that wrap around vessels (Bindocci et al, 2017). Via the PvAPs, astrocytes control several brain vascular functions, including the integrity of the blood-brain barrier, the homeostasis between the brain and the immune system, the transfer of metabolites and the regulation of cerebral blood flow (Alvarez et al, 2013;Cohen-Salmon et al, 2020). As in PAPs, most of the astrocytes' perivascular functions rely on a specific molecular repertoire that is enriched in PvAPs (Cohen-Salmon et al, 2020).…”

“…Via the PvAPs, astrocytes control several brain vascular functions, including the integrity of the blood-brain barrier, the homeostasis between the brain and the immune system, the transfer of metabolites and the regulation of cerebral blood flow (Alvarez et al, 2013;Cohen-Salmon et al, 2020). As in PAPs, most of the astrocytes' perivascular functions rely on a specific molecular repertoire that is enriched in PvAPs (Cohen-Salmon et al, 2020). For instance, the water channel aquaporin 4 and the inward-rectifying potassium channel Kir4.1 have critical roles in the regulation of perivascular homeostasis (Amiry-Moghaddam and Ottersen, 2003;Cohen-Salmon et al, 2020).…”

“…As in PAPs, most of the astrocytes' perivascular functions rely on a specific molecular repertoire that is enriched in PvAPs (Cohen-Salmon et al, 2020). For instance, the water channel aquaporin 4 and the inward-rectifying potassium channel Kir4.1 have critical roles in the regulation of perivascular homeostasis (Amiry-Moghaddam and Ottersen, 2003;Cohen-Salmon et al, 2020). Interestingly, PvAPs are sometimes contiguous with PAPs; this proximity might be critical for coupling the neuronal and vascular activities of astrocytes (Boulay et al, 2017) (Fig.…”

Role of astroglial Connexin 43 in pneumolysin cytotoxicity and during pneumococcal meningitis

“…Other cell types forming the neurovascular unit regulate the BBB function [4,5]. Among these, astrocytes, the most abundant cells of the Central Nervous System (CNS), form glial heterogeneous networks in various brain compartments that regulate neural and vascular functions, in particular BBB maturation and maintenance [6][7][8]. Astrocytes may regulate the BBB function through signaling controlling the tightness endothelial cell junctions [9].…”