Completed Brain & Nervous System Heart, Stroke & Blood

Homeostatic monitoring and control of regional brain blood flow

Funder Wellcome Charity-funded
Recipient organisation University College London
Funding £1.3M
Period Sept 2016 — Aug 2021

In plain English

AI plain-English summary

The brain must match blood supply to local activity second by second, but the cellular sensors that trigger this adjustment remain unknown. This programme will identify the specific molecules and cells that detect rising carbon dioxide, falling oxygen, and drops in blood pressure inside the brain—signals that normally instruct blood vessels to dilate or constrict. Without these homeostatic mechanisms, active brain regions risk oxygen starvation, and the BOLD signal used in fMRI scans becomes impossible to interpret reliably. The researchers will genetically disable candidate signalling pathways in rats and mice, then watch the neurovascular interface in real time using two-photon microscopy. If they succeed, the work will reveal the fundamental biology of how the brain manages its own fuel supply. This is primarily curiosity-driven fundamental science with no immediate clinical application, but the same mechanisms that regulate blood flow in health are disrupted in stroke, dementia, and small vessel disease. A precise molecular map of these sensors could eventually point toward drug targets for conditions where cerebral blood flow regulation fails.

View original technical description
This research programme is designed to explore cellular and molecular mechanisms underlying homeostatic metabolic control of regional brain blood flow by addressing the following fundamental questions: (Q1) How are the changes in brain parenchymal PCO2/[H+] detected and what are the mechanisms underlying the effect of CO2/H+ on cerebral vasculature? (Q2) What are the mechanisms responsible for hypoxia-induced dilation of cerebral vasculature and what is their role in the redistribution of regional brain blood flow in accord with parenchymal O2 content? (Q3) What is the role of CO2/H+-sensitive mechanisms of astroglial/vascular interface in neuronal activity-dependent control of cerebral vasculature and in generation of the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signals? (Q4) What are the cellular identity, sensory transduction mechanism and physiological role of an intracranial baroreceptor capable of sensing decreases in brain perfusion pressure? These questions are addressed by genetic targeting and blockade of hypothesized signalling pathways, in vivo two-photon excitation imaging of neurovascular interface ([Ca2+]i in astrocytes/neurones and parenchymal vasculature) and assessment of regional cerebral blood flow and cerebrovascular reactivity using BOLD and arterial spin labelling fMRI in experimental animals (rats and mice).

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Researchers

Alexander Gourine (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Understanding regulation of brain energy metabolism
Control of circulation by intracranial baroreceptors (Ms Philippa Chapman)
New methods for assessing the control of blood flow in the brain
Diversity in blood flow control to the brain: moving from individualized modelling towards personalized treatment of the injured brain
Dynamics of Blood Flow Control in the Brain

Original classification

Senior Research Fellowship Basic Renewal

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.