Intravital Two-Photon Microscopy and the Glymphatic System: Settling the Bulk Flow Debate
Publisher
The University of Arizona.Rights
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction, presentation (such as public display or performance) of protected items is prohibited except with permission of the author.Abstract
The glymphatic system, also known as the paravascular system, is a recently discovered physiological pathway that clears wastes and metabolites from the brain via flow of cerebrospinal fluid (CSF) and interstitial fluid (ISF). The nature of the driving force behind CSF and ISF flow is a hot topic of debate, as some groups suggest there is bulk flow driven by arterial pulsations and/or vis a tergo CSF production from the chorid plexus, and other groups postulate diffusion or dispersion occurs in the absence of bulk flow. In vivo observation of the paravascular system is particularly challenging to accomplish and usually involves injection of fluorophores directly into the Cisterna Magna or into the interstitial space so fluorescence microscopy can take place. Opponents of this method of dye delivery state that direct injection affects intracranial pressure and disrupts the natural fluid dynamics of the system. The work conducted in this thesis introduces a new paradigm of dye delivery via focus ultrasound mediated blood brain barrier disruption, which allows the fluid dynamics of the glymphatic system to be observed undisrupted using intravital two-photon microscopy. Preliminary analysis of the images suggests that bulk flow is not present at a depth of approximately 60-120 microns from the surface of the cortex and that diffusion is the major driving force in the paravascular system. Further work needs to be done in order to support this claim enough to reject the bulk flow hypothesis at all depths of the brain.Type
textElectronic Thesis
Degree Name
M.S.Degree Level
mastersDegree Program
Graduate CollegeOptical Sciences