Varner, Erika
(2017)
Dexamethasone Enhanced Microdialysis for Extended Intracranial Chemical Monitoring.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
Microdialysis is a popular method for real-time monitoring of neurotransmitters in the brain, applicable for a variety of research areas. Nonetheless, insertion of the probe into the brain tissue results in a penetration injury that triggers ischemia, activates astrocytes and microglia, and damages neurons in the surrounding area. This insertion injury significantly affects the ability of the microdialysis probe to collect samples from the surrounding tissue, a consequence that is further exacerbated with time. Incorporating dexamethasone, a glucocorticoid anti-inflammatory steroid, into the microdialysis perfusion fluid is a simple yet effective strategy for mitigating the probe insertion injury. The benefits of dexamethasone retrodialysis for long-term sampling from the rat brain are presented herein.
First, stimulated dopamine release was monitored with fast scan cyclic voltammetry next to and at the outlet of microdialysis probes at 4 hours, 24 hours, and 5 days after probe insertion into the rat striatum. Perfusing the microdialysis probe with dexamethasone and allowing the tissue 5 days to recover reinstated normal evoked dopamine activity adjacent to the probe. This provided quantitative agreement between responses measured directly in the striatal tissue and those measured at the probe outlet.
Second, transient changes in K+ and glucose were monitored in the rat cortex following the induction of spreading depolarization at 2 hours, 5 days, and 10 days after probe insertion. At all three time points the retrodialysis of dexamethasone improved the detection of K+ and glucose transients following spreading depolarization. When microdialysis probes were implanted for 5 days without dexamethasone the glucose responses became essentially undetectable, however 5 days of dexamethasone retrodialysis preserved consistent glucose responses at both 5 and 10 days after probe insertion. For the 10 day study dexamethasone was removed from the perfusion fluid on day 5, showing the benefits of dexamethasone outlast the retrodialysis itself.
The significance of enhancing microdialysis through anti-inflammatory mitigation strategies extends beyond the analytes and conditions investigated thus far. The ability to accurately and reproducibly quantify neurochemicals days after microdialysis probe implantation is invaluable and will aid in improving our understanding of the complex chemical events occurring in the brain.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
28 September 2017 |
| Date Type: |
Publication |
| Defense Date: |
27 June 2017 |
| Approval Date: |
28 September 2017 |
| Submission Date: |
7 July 2017 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
117 |
| 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, Dexamethasone, Tissue Response, Dopamine, Spreading Depolarization |
| Date Deposited: |
29 Sep 2017 01:03 |
| Last Modified: |
29 Sep 2017 01:03 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/32713 |
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