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Title: Pericyte-mediated regulation of cerebral and coronary blood flow in health and disease
Author: O'Farrell, F. M.
ISNI:       0000 0004 8503 7602
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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The information processing power of the brain is constrained by its energy supply. Neuronal activity evokes local increases in blood flow to fuel signalling by active neurons. Recent evidence has overturned the dogma that brain blood flow is principally regulated by smooth muscle-covered arterioles. Instead, contractile pericytes on brain capillaries are the first responders to neuronal activity, dilating to supply nutrients in a process called functional hyperaemia. In this thesis, I have characterised the anatomical properties of brain capillary pericytes, their surface marker expression, and their interactions with other cells in the neurovascular unit. I probed the signaling pathways underlying capillary level neurovascular coupling in acute brain slices. Adrenergic compounds induced pericyte constriction. The neuron and astrocyte-derived vasoactive messengers nitric oxide and prostaglandin E2 dilated capillaries near pericytes, as did electrical stimulation of axons, mimicking neuronal activity. During ischaemia, I found that capillaries were rapidly constricted by pericytes, which subsequently died in a state of rigor, possibly underlying the no-reflow phenomenon encountered after stroke. Blocking voltage-gated calcium channels and inhibiting the synthesis of the vasoconstrictor 20-HETE significantly delayed the ischaemia-induced constriction. Capillaries also constricted following ischaemia in vivo. Given the similar lack of reperfusion seen in the heart after myocardial infarction, I investigated the anatomy and pathophysiology of cardiac pericytes. I discovered that pericytes are abundant on coronary capillaries and share many morphological properties with brain pericytes, suggesting they might play a role in coronary blood flow regulation as well as in coronary no-reflow after heart attack.
Supervisor: Attwell, D. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available