Bidirectional control of CNS capillary diameter by pericytes
Open accessAbstract
Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at approximately 2 microm s(-1) to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.
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Vascular dilation and constriction regulate the initial step of glucose and oxygen delivery.
“For example, vascular dilation and constriction regulate the initial step of glucose and oxygen delivery2,14.”
From Energy paradox in REM sleep: balancing supply and consumption in brain metabolism (2026) · cites this paper as [14]
The paper’s Abstract says blood-flow control may be initiated at the capillary level and reports pericyte-mediated constriction and dilation of capillaries. It does not establish that these diameter changes regulate the initial step of glucose and oxygen delivery specifically. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA subset of pericytes on capillary walls is contractile, and these are the only contractile cells on capillaries.
“A subset of pericytes on capillary walls is contractile (these are the only contractile cells on capillaries (18))”
From Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes (2019) · cites this paper as [18]
Contractile pericytes can alter cerebral blood flow by adjusting their contractile tone.
“can alter cerebral blood flow by adjusting their contractile tone (18–20).”
From Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes (2019) · cites this paper as [18]
It is pericytes that constrict capillaries in human patients depositing Aβ.
“These data, and the fact that no other cells on capillaries show contractile activity (18), imply that it is pericytes that constrict capillaries in human patients depositing Aβ.”
From Amyloid β oligomers constrict human capillaries in Alzheimer's disease via signaling to pericytes (2019) · cites this paper as [18]
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Cudmore, R. H., Dougherty, S. E., & Linden, D. J. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x16682508 · Cited by 54 · see citing works
Pericytes: Problems and Promises for CNS Repair
Laredo, F., Plebanski, J., & Tedeschi, A. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00546 · Cited by 44 · see citing works
“Pericytes play a role in regulating cerebral blood flow by acting on capillaries (Peppiatt et al., 2006).”
BackgroundGoncalves, A., & Antonetti, D. A. (2022) · Fluids and Barriers of the CNS · doi:10.1186/s12987-022-00386-0 · Cited by 22 · see citing works
Plastic vasomotion entrainment
Sasaki, D., Imai, K., Ikoma, Y., & Matsui, K. (2024) · eLife · doi:10.7554/elife.93721.3 · Cited by 6 · see citing works
Energy paradox in REM sleep: balancing supply and consumption in brain metabolism
Takahashi, Y., Ikoma, Y., & Matsui, K. (2026) · Communications Biology · doi:10.1038/s42003-026-10646-6 · Cited by 1 · see citing works
“Forexample,vasculardilationandconstrictionregulatethe initialstepofglucoseandoxygendelivery 2,14 .”
- Authors
- Peppiatt, C. M., Howarth, C., Mobbs, P., & Attwell, D.
- Affiliations
- University College London (GB)
- Corresponding author
- Attwell, David
- Venue
- Nature
- Published
- 2006-10
- Volume
- 443
- Issue
- 7112
- Pages
- 700-704
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC1761848
- OpenAlex
- W2069929255
- Cited by
- 1,150
- References
- 32
- Citations by year
- 2026: 41 · 2025: 51 · 2024: 70 · 2023: 58 · 2022: 68 · 2021: 89 · 2020: 81 · 2019: 77 · 2018: 53 · 2017: 62 · 2016: 62 · 2015: 64 · 2014: 62 · 2013: 63 · 2012: 66
- FWCI
- 20.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Wellcome Trust (017948, 075232/Z/04/Z)
- Royal Society
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- pericytes, capillary diameter, blood flow regulation, cerebrovascular smooth muscle, norepinephrine, ATP, glutamate, GABA receptors, capillary constriction, retina, cerebellum, ischemia, functional neuroimaging, BOLD signal, cerebrovascular disease
- MeSH terms
- Adenosine Triphosphate, Animals, Arterioles, Calcium, Capillaries, Cerebellum, Electric Stimulation, gamma-Aminobutyric Acid, Ischemia, Neuroglia, Norepinephrine, Retina, Retinal Vessels, Vasoconstriction, Receptors, GABA, Calcium Signaling, Pericytes, Rats, In Vitro Techniques
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