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Development of zebrafish and computational models of neurovascular coupling in health and disease

Chhabria, Karishma (2018) Development of zebrafish and computational models of neurovascular coupling in health and disease. PhD thesis, University of Sheffield.

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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.

Item Type: Thesis (PhD)
Academic Units: The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Medicine (Sheffield)
Depositing User: Karishma Chhabria
Date Deposited: 11 Feb 2019 10:35
Last Modified: 11 Feb 2019 10:35
URI: http://etheses.whiterose.ac.uk/id/eprint/22833

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