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Capillary pericytes regulate cerebral blood flow in health and disease

Author

Listed:
  • Catherine N. Hall

    (Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK)

  • Clare Reynell

    (Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK)

  • Bodil Gesslein

    (University of Copenhagen, DK-2200 Copenhagen N, Denmark)

  • Nicola B. Hamilton

    (Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK)

  • Anusha Mishra

    (Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK)

  • Brad A. Sutherland

    (Acute Stroke Programme, University of Oxford, Oxford OX3 9DU, UK)

  • Fergus M. O’Farrell

    (Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK)

  • Alastair M. Buchan

    (Acute Stroke Programme, University of Oxford, Oxford OX3 9DU, UK)

  • Martin Lauritzen

    (University of Copenhagen, DK-2200 Copenhagen N, Denmark
    Glostrup University Hospital, DK-2600 Glostrup, Denmark)

  • David Attwell

    (Physiology and Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK)

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.

Suggested Citation

  • Catherine N. Hall & Clare Reynell & Bodil Gesslein & Nicola B. Hamilton & Anusha Mishra & Brad A. Sutherland & Fergus M. O’Farrell & Alastair M. Buchan & Martin Lauritzen & David Attwell, 2014. "Capillary pericytes regulate cerebral blood flow in health and disease," Nature, Nature, vol. 508(7494), pages 55-60, April.
    • Handle: RePEc:nat:nature:v:508:y:2014:i:7494:d:10.1038_nature13165
    DOI: 10.1038/nature13165
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    Cited by:

    1. Airi Jo-Watanabe & Toshiki Inaba & Takahiro Osada & Ryota Hashimoto & Tomohiro Nishizawa & Toshiaki Okuno & Sayoko Ihara & Kazushige Touhara & Nobutaka Hattori & Masatsugu Oh-Hora & Osamu Nureki & Tak, 2024. "Bicarbonate signalling via G protein-coupled receptor regulates ischaemia-reperfusion injury," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Kristen Tgavalekos & Thao Pham & Nishanth Krishnamurthy & Angelo Sassaroli & Sergio Fantini, 2019. "Frequency-resolved analysis of coherent oscillations of local cerebral blood volume, measured with near-infrared spectroscopy, and systemic arterial pressure in healthy human subjects," PLOS ONE, Public Library of Science, vol. 14(2), pages 1-27, February.
    3. Andrée-Anne Berthiaume & Franca Schmid & Stefan Stamenkovic & Vanessa Coelho-Santos & Cara D. Nielson & Bruno Weber & Mark W. Majesky & Andy Y. Shih, 2022. "Pericyte remodeling is deficient in the aged brain and contributes to impaired capillary flow and structure," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    4. Mohammad Haft-Javaherian & Linjing Fang & Victorine Muse & Chris B Schaffer & Nozomi Nishimura & Mert R Sabuncu, 2019. "Deep convolutional neural networks for segmenting 3D in vivo multiphoton images of vasculature in Alzheimer disease mouse models," PLOS ONE, Public Library of Science, vol. 14(3), pages 1-21, March.
    5. Domenic H. Cerri & Daniel L. Albaugh & Lindsay R. Walton & Brittany Katz & Tzu-Wen Wang & Tzu-Hao Harry Chao & Weiting Zhang & Randal J. Nonneman & Jing Jiang & Sung-Ho Lee & Amit Etkin & Catherine N., 2024. "Distinct neurochemical influences on fMRI response polarity in the striatum," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Satoshi Ii & Hiroki Kitade & Shunichi Ishida & Yohsuke Imai & Yoshiyuki Watanabe & Shigeo Wada, 2020. "Multiscale modeling of human cerebrovasculature: A hybrid approach using image-based geometry and a mathematical algorithm," PLOS Computational Biology, Public Library of Science, vol. 16(6), pages 1-28, June.
    7. Adam Institoris & Milène Vandal & Govind Peringod & Christy Catalano & Cam Ha Tran & Xinzhu Yu & Frank Visser & Cheryl Breiteneder & Leonardo Molina & Baljit S. Khakh & Minh Dang Nguyen & Roger J. Tho, 2022. "Astrocytes amplify neurovascular coupling to sustained activation of neocortex in awake mice," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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