TRPV4 in the Choroid Plexus Epithelium - Preston D.pdf (2.61 MB)

TRPV4 in the Choroid Plexus Epithelium: Pathway Analysis and Implications for Cerebrospinal Fluid Production

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thesis
posted on 03.12.2019 by Daniel Christopher Preston
Hydrocephalus is a disease characterized by an increase in cerebrospinal fluid (CSF) in the ventricles of the brain. This manifests as a result of either overproduction or underabsorption of CSF leading to increases in pressure, swelling and loss of brain matter. Current treatments for this disease include surgical interventions via the introduction of shunts or endoscopic third ventriculostomy, both of which aim to redirect flow of CSF in to another cavity for absorption. Limited pharmacotherapies are available in the treatment of hydrocephalus, and there exists a clinical need for drug therapies, which can ameliorate the pathophysiology associated with hydrocephalus and ventriculomegaly. CSF is produced primarily by the choroid plexus (CP), found in the ventricles of the brain. Composed of a high resistance epithelium surrounding a capillary network, the CP epithelium acts as a barrier, regulating ion transport between the CSF and blood. This thesis describes mechanisms by which TRPV4 may stimulate the transepithelial movement of ions across the CP epithelium, resulting in the production of cerebrospinal fluid. The roles of Calcium-activated potassium channels, calcium-activated chloride channels, sodium-potassium-chloride cotransporters and regulatory enzymes in this mechanistic pathway are explored.

History

Degree Type

Master of Science

Department

Biological Sciences

Campus location

Indianapolis

Advisor/Supervisor/Committee Chair

Bonnie Blazer-Yost

Additional Committee Member 2

Teri Belecky-Adams

Additional Committee Member 3

James Clack

Additional Committee Member 4

Nick Berbari

Licence

Exports