Capillary pericytes regulate cerebral blood flow in health and disease

Catherine N. Hall, Clare Reynell, Bodil Gesslein, Nicola B. Hamilton, Anusha Mishra, Brad A. Sutherland, Fergus M. Oâ Farrell, Alastair M. Buchan, Martin Lauritzen, David Attwell

Research output: Contribution to journalArticle

564 Citations (Scopus)

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 E 2, 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.

Original languageEnglish (US)
Pages (from-to)55-60
Number of pages6
JournalNature
Volume508
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

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Cerebrovascular Circulation
Pericytes
Health
Arterioles
Constriction
Prostaglandins E
Blood-Brain Barrier
Smooth Muscle
Neurotransmitter Agents
Dilatation
Glutamic Acid
Nitric Oxide
Ischemia
Stroke
Pathology
Oxygen
Neurons
Brain

ASJC Scopus subject areas

  • General

Cite this

Hall, C. N., Reynell, C., Gesslein, B., Hamilton, N. B., Mishra, A., Sutherland, B. A., ... Attwell, D. (2014). Capillary pericytes regulate cerebral blood flow in health and disease. Nature, 508(1), 55-60. https://doi.org/10.1038/nature13165

Capillary pericytes regulate cerebral blood flow in health and disease. / Hall, Catherine N.; Reynell, Clare; Gesslein, Bodil; Hamilton, Nicola B.; Mishra, Anusha; Sutherland, Brad A.; Oâ Farrell, Fergus M.; Buchan, Alastair M.; Lauritzen, Martin; Attwell, David.

In: Nature, Vol. 508, No. 1, 2014, p. 55-60.

Research output: Contribution to journalArticle

Hall, CN, Reynell, C, Gesslein, B, Hamilton, NB, Mishra, A, Sutherland, BA, Oâ Farrell, FM, Buchan, AM, Lauritzen, M & Attwell, D 2014, 'Capillary pericytes regulate cerebral blood flow in health and disease', Nature, vol. 508, no. 1, pp. 55-60. https://doi.org/10.1038/nature13165
Hall CN, Reynell C, Gesslein B, Hamilton NB, Mishra A, Sutherland BA et al. Capillary pericytes regulate cerebral blood flow in health and disease. Nature. 2014;508(1):55-60. https://doi.org/10.1038/nature13165
Hall, Catherine N. ; Reynell, Clare ; Gesslein, Bodil ; Hamilton, Nicola B. ; Mishra, Anusha ; Sutherland, Brad A. ; Oâ Farrell, Fergus M. ; Buchan, Alastair M. ; Lauritzen, Martin ; Attwell, David. / Capillary pericytes regulate cerebral blood flow in health and disease. In: Nature. 2014 ; Vol. 508, No. 1. pp. 55-60.
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