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Title: Development of zebrafish and computational models of neurovascular coupling in health and disease
Author: Chhabria, Karishma
ISNI:       0000 0004 7655 3728
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2018
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In this thesis, I have developed a novel zebrafish model of neurovascular coupling. Combining lightsheet imaging, compound transgenic zebrafish models and custom MATLAB based analysis pipelines, I characterised the neurovascular responses (neuronal calcium increases and change in red blood cell speed) in the optic tectum in response to visual stimulation. I determined the development stage at which neurovascular coupling in zebrafish larvae develops, followed by testing the requirement for nitric oxide or astrocyte cyclo-oxygenase in my model. I then used this model to investigate factors influencing neurovascular function. I first characterized the effect of glucose exposure and the role of nitric oxide in modulating neurovascular coupling. I then examined the effect of genetic mutation of Guanosine Triphosphate cyclohydrolase (an enzyme involved in nitric oxide and dopamine production in the brain) on neurovascular coupling. Finally, I have developed a minimal mathematical model of the neurovascular unit. To demonstrate the potential of this model I have simulated the effect of high blood glucose and low nitric oxide on neurovascular coupling and show this conforms with experimental data obtained in zebrafish.
Supervisor: Chico, Tim ; Howarth, Clare Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available