Robbins, Elaine
(2019)
Advancing Methods for In Vivo Neurochemical Monitoring.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Dopamine is a neurotransmitter involved in both normal and pathological brain function. Modeling dopamine responses measured with fast scan cyclic voltammetry can provide insight into dopamine’s function. Dopamine responses are broadly categorized as fast and slow, based on the amount of time between when the stimulus starts and when dopamine is detected. By changing the amount of time between a stimulus pulse and a dopamine-detecting waveform, we determined that slow-responding sites are due to differences in kinetics between fast and slow sites, not a gap between the recording electrode and dopamine terminals. Additionally, with the use of the D2 antagonist raclopride and advances in the restricted diffusion model for dopamine dynamics, we show that slow sites are caused by an underlying autoinhibitory tone that fast sites do not have.
In addition, this work explores metabolic changes after traumatic brain injury. Traumatic brain injury is divided into a primary insult and a secondary injury, like spreading depolarization, that causes further damage over time. Spreading depolarizations – waves of uncontrolled depolarization followed by energy-consuming repolarization – can cause the injury lesion core to spread into the comparatively healthy surrounding tissue. Monitoring glucose and potassium as markers of spreading depolarization waves can be accomplished by microdialysis; however, immune response to the injury caused by implantation greatly diminishes the temporal sampling window. Previous work has established that five days of retrodialysis with dexamethasone mitigates this immune response and greatly increases the probe lifetime. Traumatic brain injury model rats and rapid sampling microdialysis were employed to monitor glucose and potassium levels continuously for ten days after injury. Short term metabolic crises, like spreading depolarization, were observed in injured animals. Additionally, in almost every case, glucose concentrations declined slowly over several days to undetectable levels and did not recover during the timespan of the experiment, despite histology confirming that there is living tissue around the probe ten days after implantation.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
25 September 2019 |
| Date Type: |
Publication |
| Defense Date: |
26 July 2019 |
| Approval Date: |
25 September 2019 |
| Submission Date: |
29 July 2019 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
105 |
| 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: |
Dopamine, Fast scan cyclic voltammetry, Modeling, Glucose, Traumatic brain injury, Spreading depolarization |
| Date Deposited: |
25 Sep 2019 16:01 |
| Last Modified: |
25 Sep 2019 16:01 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/37230 |
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