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Capillary pericytes regulate cerebral blood flow in health and disease
journal contribution
posted on 2023-05-19, 00:33 authored by Hall, CN, Reynell, C, Gesslein, B, Hamilton, NB, Mishra, A, Brad SutherlandBrad Sutherland, O'Farrell, FM, Buchan, AM, Lauritzen, M, Attwell, DBrain blood flow increases, evoked by neuronal activity, power neural computation and are the basis of BOLD functional imaging. It is controversial whether blood flow is controlled solely by arteriole smooth muscle, or also by capillary pericytes. 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 which damages neurons after stroke.
History
Publication title
NatureVolume
508Issue
7494Pagination
55-60ISSN
0028-0836Department/School
Tasmanian School of MedicinePublisher
Nature Publishing GroupPlace of publication
United KingdomRights statement
Copyright 2014 Macmillan Publishers Limited.Repository Status
- Restricted