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Astrocytes: Orchestrators of brain gas exchange and oxygen homeostasis.

ABSTRACT: If we consider neurons like muscles during exercise, the demand for oxygen (O₂) and carbon dioxide (CO₂) elimination is constantly changing. This review summarises the evidence that astrocytes are essential for homeostasis of the respiratory gases in the brain, with a particular focus on oxygen homeostasis. Astrocytes surround cerebral blood vessels and sense changes in oxygen availability in the milieu. They contribute to pH homeostasis and are increasingly recognized for their contribution to central chemosensitivity, particularly in detecting changes in CO₂ and proton (H⁺) concentrations. They are one of the cell types that govern changes in cerebral perfusion rate. Cerebral perfusion dynamically matches tissue metabolism, to balance O₂ delivery and CO₂ removal. By examining the role of astrocytes as both sensors and effectors in this homeostatic balancing act, this review argues that astrocytes influence the metabolic environment of neural networks with profound implications for cognitive function.

SUBMITTER: Christie IN

PROVIDER: S-EPMC7618565 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature

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Astrocytes: Orchestrators of brain gas exchange and oxygen homeostasis.

Christie Isabel N IN

The Journal of physiology 20250825 4

If we consider neurons like muscles during exercise, the demand for oxygen (O<sub>2</sub>) and carbon dioxide (CO<sub>2</sub>) elimination is constantly changing. This review summarises the evidence that astrocytes are essential for homeostasis of the respiratory gases in the brain, with a particular focus on oxygen homeostasis. Astrocytes surround cerebral blood vessels and sense changes in oxygen availability in the milieu. They contribute to pH homeostasis and are increasingly recognized for ...[more]

PMID: 40853771

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Project description:Background: HIV infection is associated with impaired gas transfer in the lung as indicated by a low diffusing capacity (DLCO). Mechanisms for reduced DLCO in the setting of HIV infection are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood gene expression. Methods: A total of 40 HIV-infected (HIV+) and uninfected (HIV-) men with preserved versus reduced DLCO were selected from a larger cohort study of lung function. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from peripheral blood leukocytes (PBLs) and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV+ vs. HIV- subjects with preserved DLCO and those with impaired DLCO to identify differentially activated pathways. Results: Using pathway-based analyses we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and apoptosis. When we applied a similar analysis to subjects with low DLCO, we identified a much broader repertoire of inflammatory and immune-related pathways in HIV+ patients relative to HIV- subjects, with up-regulation of multiple interleukin pathways, interferon signaling, Toll-like receptor signaling, and T cell/B cell receptor signaling. We confirmed elevated circulating levels of IL-6 in HIV+ patients with reduced DLCO relative to the other groups. Conclusions: Our findings reveal that PBLs of subjects with HIV infection and low DLCO are distinguished by widespread enrichment of immuno-inflammatory programs. Activation of these pathways may alter the biology of circulating leukocytes and play a role in the pathogenesis of HIV-associated pulmonary gas exchange impairment. Total RNA was isolated from peripheral blood leukocytes in four subject groups: 1. HIV-, low DLCO (N = 11); 2. HIV+, low DLCO (N = 10); 3. HIV-, preserved DLCO (N = 9); 4. HIV+, preserved DLCO (N = 9). Each sample was hybridized to an Affymetrix PrimeView Human Gene Expression microarray for a total of 39 experiments.

Dataset Information

Astrocytes: Orchestrators of brain gas exchange and oxygen homeostasis.

Publications

Astrocytes: Orchestrators of brain gas exchange and oxygen homeostasis.

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