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BrainEnergy SIGNED

Control of cerebral blood flow by capillary pericytes in health and disease

Total Cost €

0

EC-Contrib. €

0

Partnership

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 BrainEnergy project word cloud

Explore the words cloud of the BrainEnergy project. It provides you a very rough idea of what is the project "BrainEnergy" about.

treating    pathology    ischaemia    lies    tissue    occluded    health    live    reperfuse    dilation    flow    located    causes    artery    sinister    blood    patients    pericyte    prelude    decrease    barrier    relative    patch    immunohistochemistry    tone    rigor    supply    alzheimer    diseases    physiologically    carers    intervals    controllers    economic    constriction    upstream    diabetes    damages    astrocytes    injury    extend    spinal    neuronal    successfully    disease    neurons    mathematical    little    regulating    energy    therapies    imaging    suffering    degrades    death    pericytes    mechanisms    rodent    clamping    constrict    preventing    block    suffers    enormous    neurosurgery    causing    ing    stroke    vessel    phenomenon    capillary    reflow    normally    therapeutic    contributions    reperfused    optogenetics    despite    function    shown    die    reduces    dilate    signalling    cord    probably    revealed    photon    lasting    human    diameter    local    microglia    brain    capillaries   

Project "BrainEnergy" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY COLLEGE LONDON 

Organization address
address: GOWER STREET
city: LONDON
postcode: WC1E 6BT
website: n.a.

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 2˙499˙954 €
 EC max contribution 2˙499˙954 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2022-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON UK (LONDON) coordinator 2˙499˙954.00

Map

 Project objective

Pericytes, located at intervals along capillaries, have recently been revealed as major controllers of brain blood flow. Normally, they dilate capillaries in response to neuronal activity, increasing local blood flow and energy supply. But in pathology they have a more sinister role. After artery block causes a stroke, the brain suffers from the so-called “no-reflow” phenomenon - a failure to fully reperfuse capillaries, even after the upstream occluded artery has been reperfused successfully. The resulting long-lasting decrease of energy supply damages neurons. I have shown that a major cause of no-reflow lies in pericytes: during ischaemia they constrict and then die in rigor. This reduces capillary diameter and blood flow, and probably degrades blood-brain barrier function. However, despite their crucial role in regulating blood flow physiologically and in pathology, little is known about the mechanisms by which pericytes function.

By using blood vessel imaging, patch-clamping, two-photon imaging, optogenetics, immunohistochemistry, mathematical modelling, and live human tissue obtained from neurosurgery, this programme of research will: (i) define the signalling mechanisms controlling capillary constriction and dilation in health and disease; (ii) identify the relative contributions of neurons, astrocytes and microglia to regulating pericyte tone; (iii) develop approaches to preventing brain pericyte constriction and death during ischaemia; (iv) define how pericyte constriction of capillaries and pericyte death contribute to Alzheimer’s disease; (v) extend these results from rodent brain to human brain pericytes as a prelude to developing therapies.

The diseases to which pericytes contribute include stroke, spinal cord injury, diabetes and Alzheimer’s disease. These all have an enormous economic impact, as well as causing great suffering for patients and their carers. This work will provide novel therapeutic approaches for treating these diseases.

 Publications

year authors and title journal last update
List of publications.
2018 Christian Madry, I. Lorena Arancibia-Cárcamo, Vasiliki Kyrargyri, Victor T. T. Chan, Nicola B. Hamilton, David Attwell
Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion
published pages: E1608-E1617, ISSN: 0027-8424, DOI: 10.1073/pnas.1715354115
Proceedings of the National Academy of Sciences 115/7 2019-05-16
2018 Jinping Cheng, Nils Korte, Ross Nortley, Huma Sethi, Yamei Tang, David Attwell
Targeting pericytes for therapeutic approaches to neurological disorders
published pages: , ISSN: 0001-6322, DOI: 10.1007/s00401-018-1893-0
Acta Neuropathologica 2019-05-16
2017 Ross Nortley, David Attwell
Control of brain energy supply by astrocytes
published pages: 80-85, ISSN: 0959-4388, DOI: 10.1016/j.conb.2017.09.012
Current Opinion in Neurobiology 47 2019-05-16
2016 Anusha Mishra, James P Reynolds, Yang Chen, Alexander V Gourine, Dmitri A Rusakov, David Attwell
Astrocytes mediate neurovascular signaling to capillary pericytes but not to arterioles
published pages: 1619-1627, ISSN: 1097-6256, DOI: 10.1038/nn.4428
Nature Neuroscience 19/12 2019-05-16
2019 Pablo Izquierdo, David Attwell, Christian Madry
Ion Channels and Receptors as Determinants of Microglial Function
published pages: 278-292, ISSN: 0166-2236, DOI: 10.1016/j.tins.2018.12.007
Trends in Neurosciences 42/4 2019-05-16

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The information about "BRAINENERGY" are provided by the European Opendata Portal: CORDIS opendata.

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