Bidirectional control of CNS capillary diameter by pericytes

By C. Peppiatt, Clare Howarth, P. Mobbs, David Attwell. Nature, 2006

1,131 citations recorded by the source corpus.

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 ∼2 µm 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 (γ-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.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology, Neurology

View Paper: https://www.semanticscholar.org/paper/ff5054dc29e142e7cd536f2d4771c922a9fcf2b1

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Citations in the corpus

A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity (2020, background): “In particular, ACs are believed to play a decisive role in maintaining the barrier function of the brain microcapillary ECs and in controlling the CBF [2].”
Ischemia/Reperfusion (2016, neutral): “endothelium-dependent, peroxynitrite-mediated mechanism (317, 631, 882).”
Cell Biology of Ischemia/Reperfusion Injury (2012, background): “Indeed, pericytes have been shown to constrict capillaries shortly after the onset of retinal or cerebral ischemia and remain contracted when blood flow is reinstituted (Peppiatt et al., 2006; Yemisci et al., 2009).”
The blood-brain barrier in Alzheimer's disease (2017, positive): “Pericytes also maintain the structural stability of microvessels, clear the CNS of toxic cellular byproducts, and regulate the blood ﬂ ow through brain capillaries by controlling cellular contraction/relaxation (Peppiatt et al., 2006; Dore-Duffy, 2008; Sagare et al., 2013).”
The blood-brain barrier. (2015, background): “These cells contain contractile proteins, and have the ability to contract to control the diameter of the capillary (Peppiatt et al. 2006; Hall et al. 2014).”
Regulation of retinal blood flow in health and disease. (2008, background): “They are able to regulate the capillary diameter through contraction and relaxation (Lombard, 2006; Peppiatt et al., 2006; Yamanishi et al., 2006).”
The blood-brain barrier: an engineering perspective (2013, background): “Pericytes are contractile, with actin stress fibers throughout the cell body, and contribute to the regulation of blood flow by controlling capillary diameter (Peppiatt et al., 2006; Hamilton et al., 2010; Dalkara et al., 2011).”
Cellular and physiological mechanisms underlying blood flow regulation in the retina choroid in health disease (2012, positive): “It is well established that pericytes possess the complement of muscle contractile proteins (Herman and D’Amore, 1985) and are capable of initiating vasomotor signals that can be propagated along the length of capillaries to other pericytes (Peppiatt et al., 2006; Puro, 2007).”
The blood-brain barrier in health and chronic neurodegenerative disorders. (2008, positive): “Recent studies have shown that pericytes are contractile cells which regulate brain capillary blood flow through contraction and relaxation (Peppiatt et al., 2006).”
Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging (2010, methodology): “Quantitative image analysis, including desmin-positive pericyte coverage, NG2-positive pericyte number, lectin-positive capillary length, CD31-positive capillary length, fluorescent intensity analysis of extravascular IgG and fibrin accumulation, aquaporin-4-positive or a-syntrophin-positive astrocy”
Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury (2011, background): “…by spreading depolarization, is involved as a vasoconstrictor inducing spreading ischemia (Windmuller et al, 2005), and the vascular cells termed pericytes may contribute to capillary constrictions in normal brain tissue (Peppiatt et al, 2006) as well as in ischemic tissue (Yemisci et al, 2009).”