Glial Cells Dilate and Constrict Blood Vessels: A Mechanism of Neurovascular Coupling

By Monica R. Metea, E. A. Newman. Journal of Neuroscience, 2006

604 citations recorded by the source corpus.

Neuronal activity evokes localized changes in blood flow. Although this response, termed neurovascular coupling, is widely used to monitor human brain function and diagnose pathology, the cellular mechanisms that mediate the response remain unclear. We investigated the contribution of glial cells to neurovascular coupling in the acutely isolated mammalian retina. We found that light stimulation and glial cell stimulation can both evoke dilation or constriction of arterioles. Light-evoked and glial-evoked vasodilations were blocked by inhibitors of cytochrome P450 epoxygenase, the synthetic enzyme for epoxyeicosatrienoic acids. Vasoconstrictions, in contrast, were blocked by an inhibitor of ω-hydroxylase, which synthesizes 20-hydroxyeicosatetraenoic acid. Nitric oxide influenced whether vasodilations or vasoconstrictions were produced in response to light and glial stimulation. Light-evoked vasoactivity was blocked when neuron-to-glia signaling was interrupted by a purinergic antagonist. These results indicate that glial cells contribute to neurovascular coupling and suggest that regulation of blood flow may involve both vasodilating and vasoconstricting components.

Subfields: Biochemistry, Endocrinology, Diabetes and Metabolism, Physiology

View Paper: https://www.semanticscholar.org/paper/5c9b24a2f412a72b62a969696439091034593d9a

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Biochemistry

1. Maiken Nedergaard
2. Philip Haydon
3. David Attwell
4. Giorgio Carmignoto
5. C. Nicholson
6. E. Sykova
7. E. A. Newman
8. C. Iadecola

In Endocrinology, Diabetes and Metabolism

1. C. Nicholson
2. E. Sykova
3. B. Barres
4. Philip Haydon
5. Maiken Nedergaard
6. E. A. Newman
7. Giorgio Carmignoto
8. C. Iadecola

In Physiology

1. Maiken Nedergaard
2. Philip Haydon
3. E. A. Newman
4. Giorgio Carmignoto
5. David Attwell
6. Igor Allaman
7. B. Barres
8. Pierre J. Magistretti

Citations in the corpus

• Physiology of Astroglia. (2018, neutral): “In the retina, both effects could be observed with vasodilatation being mediated by PGE2 and EETs and vasoconstriction by 20-HETE (1110, 1127).”
• Cellular and physiological mechanisms underlying blood flow regulation in the retina choroid in health disease (2012, neutral): “fere with neurovascular coupling mechanisms (Metea and Newman, 2006).”
• Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. (2011, background): “Alternatively, arachidonic acid can diffuse in smooth muscle cells and cause vasoconstriction after its conversion in 20-hydroxyeicosatetraenoic acid (20-HETE) (Mulligan and MacVicar, 2004; Metea and Newman, 2006) (Figure 2C).”
• Astrocyte control of synaptic transmission and neurovascular coupling. (2006, background): “The ability of astrocytes to trigger also arteriole constriction has been further confirmed in whole-mounted retina preparations (135).”
• Glial regulation of the cerebral microvasculature (2007, background): “Although the astrocytic Ca 2+ response invariably precedes the vascular respons”
• Glial and neuronal control of brain blood flow (2010, positive): “The build-up of arachidonic acid leads, in turn, to the production of its metabolites, including prostaglandins and epoxyeicosatrienoic acids (EETs), which dilate nearby arteriole”
• Diffusion in Brain Extracellular Space (2008, positive): “This new community of elements has been called the “neurovascular unit” (2, 129) and provides a complex interface for substances entering, or leaving the ECS (226).”
• The mystery and magic of glia: a perspective on their roles in health and disease. (2008, background): “Astrocytes can release either vasoconstrictors or vasodilators depending on context (Zonta et al., 2003; Metea and Newman, 2006; Gordon et al., 2007), but the nature of the signals, relevant contexts, and functional significance is not yet clear.”
• Regulation of retinal blood flow in health and disease. (2008, background): “Interactions between substances, released either by endothelial or glial cells or by neurons, affect the arteriolar tone, thus regulating the retinal vasomotor responses (Fig. 10; Haefliger et al., 1994a; Brown and Jampol, 1996; Pournaras, 1996; Haefliger et al., 2001; Metea and Newman, 2006).”
• New functions of Müller cells (2013, background): “Whether vasodilating or vasoconstricting responses are produced is determined by nitric oxide (with reduced vasodilation when nitric oxide levels are increased), possibly by modulating the production of arachidonic acid metabolites (Metea and Newman, 2006; Mishra and Newman, 2010).”