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Cited by 513Barrier Structure and Function StudiesNeuroinflammation and Neurodegeneration MechanismsAdvanced MRI Techniques and Applications

Pericyte-mediated regulation of capillary diameter: a component of neurovascular coupling in health and disease

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Hamilton, Nicola B.·2010·Frontiers in Neuroenergetics
DOI 10.3389/fnene.2010.00005PMC PMC2912025
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Abstract

Because regional blood flow increases in association with the increased metabolic demand generated by localized increases in neural activity, functional imaging researchers often assume that changes in blood flow are an accurate read-out of changes in underlying neural activity. An understanding of the mechanisms that link changes in neural activity to changes in blood flow is crucial for assessing the validity of this assumption, and for understanding the processes that can go wrong during disease states such as ischaemic stroke. Many studies have investigated the mechanisms of neurovascular regulation in arterioles but other evidence suggests that blood flow regulation can also occur in capillaries, because of the presence of contractile cells, pericytes, on the capillary wall. Here we review the evidence that pericytes can modulate capillary diameter in response to neuronal activity and assess the likely importance of neurovascular regulation at the capillary level for functional imaging experiments. We also discuss evidence suggesting that pericytes are particularly sensitive to damage during pathological insults such as ischaemia, Alzheimer's disease and diabetic retinopathy, and consider the potential impact that pericyte dysfunction might have on the development of therapeutic interventions and on the interpretation of functional imaging data in these disorders.

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  • Functionally, adenosine binding to pericyte α1-adrenergic receptors activates ATP-sensitive K+ channels, causing pericyte hyperpolarization and relaxation.

    “Functionally, adenosine binding to pericyte 𝛂 1-adrenergic receptors activates ATP-sensitive K + channels causing pericyte hyperpolarization and relaxation (232).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [232]

    In “Mechanisms of metabolic regulation of pericyte tone,” the paper says adenosine activates A1 and A2A adenosine receptors, not α1-adrenergic receptors. It does support the subsequent increase in KATP channel activity and the link between hyperpolarization and dilation. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

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  • Increases in intracellular Ca2+ in response to large increases in extracellular K+ concentrations activate voltage-gated Ca2+ channels in pericytes, leading to pericyte depolarization and contraction.

    “Increases in intracellular Ca 2 + in response to large increases in extracellular K + concentrations activate voltage-gated Ca 2 + channels in pericytes, which leads to pericyte depolarization and contraction (232).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [232]

    The “Pericyte constriction” section says depolarization activates voltage-operated Ca2+ channels, raising intracellular Ca2+ and favoring contraction. It does not attribute that sequence to large increases in extracellular K+; the “Pericyte dilation” section instead says an increase in extracellular K+ can produce dilation. The claim also reverses the described order by placing the intracellular Ca2+ rise before channel activation and depolarization. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

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Cited by

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Authors
Hamilton, N. B.
Affiliations
University College London (GB)
Corresponding author
Hamilton, Nicola B.
ORCID
Hamilton, Nicola B.
Venue
Frontiers in Neuroenergetics
Publisher
Frontiers Media SA
Published
2010
Volume
2
ISSN
1662-6427 (ISSN-L)
DOI
10.3389/fnene.2010.00005
PMC
PMC2912025
OpenAlex
W2139123746
Cited by
513
References
5
Citations by year
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FWCI
13.38
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Neuroenergetics (publishedVersion, cc-by)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust
  • Research Councils UK
  • Fondation Leducq
  • Medical Research Council
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
Keywords
pericytes, capillary diameter, neurovascular coupling, neuronal activity, ischemic stroke, Alzheimer's disease, diabetic retinopathy, ischemia, functional neuroimaging, pericyte dysfunction

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