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Theoretical and Experimental Improvements for Fast Microdialysis

Ngo, Khanh (2020) Theoretical and Experimental Improvements for Fast Microdialysis. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Microdialysis is the most widely used technique for intracranial sampling. Its versatility prompts important applications, from bedside traumatic brain injury monitoring to psychological disorder treatment. However, historically microdialysis methods have a time resolution of 5-30 mins, and thus are not well suited to obtain physiological information, such as rates of extracellular processes or the relationship between neurochemical levels and behavior. Building from recent work in our laboratory, we developed instrumentation for making dopamine measurements in awake and freely moving rats over extended periods at one-minute time resolution using microdialysis sampling analyzed with online HPLC (Fast Microdialysis).
Fast Microdialysis was used to investigate the beneficial effects of the anti-inflammatory drug dexamethasone (DEX) to penetration injury caused by dialysis probe implantation. Retrodialysis of DEX was found to potentiate both basal levels and stimulated release of striatal DA. Applying Fast Microdialysis to behavioral studies necessitated creation of a rotating operant chamber. Using this device, both trained- and untrained- animal’s behavior correlated with DA release, however with different characteristics. Robust and fast determination of DA allowed for creation of new microdialysis techniques in the non-steady state regime to investigate morphology and neurotransmitter regulation. Thus, a comprehensive mathematical model was created to analyze transient responses measured by Fast Microdialysis. A robust, adaptive random sampling simplex approach was used to fit the model to transient data. Striatal tissue tortuosity, porosity and the reuptake rate constant of DA were determined from a single transient response on awake and freely moving rats.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Ngo, Khanhktn6@pitt.eduktn60000-0003-2325-5236
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWeber, Stephensweber@pitt.edusweber
Committee MemberAmemiya, Shigeruamemiya@pitt.eduamemiya
Committee MemberStar, Alexanderastar@pitt.eduastar
Committee MemberCui, Xinyanxic11@pitt.eduxic11
Date: 16 September 2020
Date Type: Publication
Defense Date: 2 July 2020
Approval Date: 16 September 2020
Submission Date: 3 June 2020
Access Restriction: 1 year -- Restrict access to University of Pittsburgh for a period of 1 year.
Number of Pages: 231
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Chemistry
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: microdialysis, HPLC, online, in vivo, dopamine
Date Deposited: 16 Sep 2020 14:38
Last Modified: 16 Sep 2020 14:38
URI: http://d-scholarship.pitt.edu/id/eprint/39476

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