title: Capillary pericytes regulate cerebral blood flow in health and disease.
abstract: Increases in brain blood flow, evoked by neuronal activity, power neural computation and form the basis of BOLD (blood-oxygen-level-dependent) functional imaging. Whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes, is controversial. We demonstrate that neuronal activity and the neurotransmitter glutamate evoke the release of messengers that dilate capillaries by actively relaxing pericytes. Dilation is mediated by prostaglandin E2, but requires nitric oxide release to suppress vasoconstricting 20-HETE synthesis. In vivo, when sensory input increases blood flow, capillaries dilate before arterioles and are estimated to produce 84% of the blood flow increase. In pathology, ischaemia evokes capillary constriction by pericytes. We show that this is followed by pericyte death in rigor, which may irreversibly constrict capillaries and damage the blood-brain barrier. Thus, pericytes are major regulators of cerebral blood flow and initiators of functional imaging signals. Prevention of pericyte constriction and death may reduce the long-lasting blood flow decrease that damages neurons after stroke.
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology University College London, Gower St., London, WC1E 6BT, UK.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Hall
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology University College London, Gower St., London, WC1E 6BT, UK.
authors.forename: Clare
authors.initials: C
authors.lastname: Reynell
authors.affiliation: Department of Neuroscience & Pharmacology and Center for Healthy Aging, and Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Bodil
authors.initials: B
authors.lastname: Gesslein
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology University College London, Gower St., London, WC1E 6BT, UK.
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Hamilton
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology University College London, Gower St., London, WC1E 6BT, UK.
authors.forename: Anusha
authors.initials: A
authors.lastname: Mishra
authors.affiliation: Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: Brad A
authors.initials: BA
authors.lastname: Sutherland
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology University College London, Gower St., London, WC1E 6BT, UK.
authors.forename: Fergus M
authors.initials: FM
authors.lastname: O'Farrell
authors.affiliation: Acute Stroke Programme, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DU, UK.
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Buchan
authors.affiliation: Department of Neuroscience & Pharmacology and Center for Healthy Aging, and Department of Clinical Neurophysiology, Glostrup Hospital, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Lauritzen
authors.affiliation: Department of Neuroscience, Physiology & Pharmacology University College London, Gower St., London, WC1E 6BT, UK.
authors.forename: David
authors.initials: D
authors.lastname: Attwell
mesh_terms: D000818:Animals; D001160:Arterioles / Q000502:physiology; D001812:Blood-Brain Barrier / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000473:pathology; D002196:Capillaries / Q000166:cytology* / Q000187:drug effects; D016923:Cell Death; D002531:Cerebellum / Q000098:blood supply; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D015232:Dinoprostone / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D059907:Functional Neuroimaging; D018698:Glutamic Acid / Q000494:pharmacology; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D020286:Pericytes / Q000166:cytology / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020521:Stroke / Q000473:pathology; D014661:Vasoconstriction; D014664:Vasodilation / Q000187:drug effects
chemical_list: D018691:Excitatory Amino Acid Antagonists; D006893:Hydroxyeicosatetraenoic Acids; D017470:Receptors, Glutamate; D009569:Nitric Oxide; D018698:Glutamic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D015232:Dinoprostone