Fine, David
(2020)
Aligning Acute and Chronic Functional Readouts and utilizing Zolpidem to improve Neurological Impairments after Cardiac Arrest.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
While cardiac arrest survival rates have improved alongside recent advances in modern resuscitation techniques and targeted temperature management, many survivors experience multiple ongoing symptoms after their hypoxic-ischemic brain injury (HIBI) including movement disorders, depression, and low cognitive arousal. Neurological assessments like the neurological deficit score (NDS), and physiological readouts from blood chemistry values are used to assess acute post-injury outcome, but little has been done to evaluate how these acute readouts distinguish heterogeneity within the injury population, or how they align with long term behavioral and neurological outcomes as a prognostic tool. Recent evidence also highlights zolpidem as an effective treatment for post-HIBI symptoms, but its clinical use has been met with mixed results. This study utilized a regression model and correlational analyses to evaluate associations among NDS, blood lactate, and blood acid base excess values as acute post-injury readouts, behavioral outcome, and dopamine neurotransmission outcomes obtained via fast scan cyclic voltammetry two weeks after a 5-min asphyxia cardiac arrest (ACA). A pilot study was also performed to evaluate the effects of chronic systemic zolpidem administration on improving behavioral outcomes and reversing striatal hyper-dopaminergia after ACA. NDS significantly aligned with survival probability after ACA. NDS and both blood chemistry readouts aligned with several behavioral and dopamine neurotransmission outcomes, and several dopaminergic and behavioral outcomes robustly correlated with one another. Additionally, chronic zolpidem reflexive and cognitive behavioral outcomes, as defined by the acoustic startle response and the sucrose preference test, respectively. This work highlights novel associations between post-HIBI behavioral and neurological outcomes as well as benefits of chronic zolpidem administration in ameliorating post-HIBI neurological sequelae. Future work should further characterize the effects of zolpidem administration after cardiac arrest and utilize molecular assays to identify protein expression changes that will unravel neurobiological mechanisms driving HIBI-induced functional impairments and highlight therapeutic targets to treat CA survivors.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
16 September 2020 |
| Date Type: |
Publication |
| Defense Date: |
22 June 2020 |
| Approval Date: |
16 September 2020 |
| Submission Date: |
27 July 2020 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
87 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Neuroscience |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
cardiac arrest, ischemia, zolpidem, dopamine |
| Date Deposited: |
16 Sep 2020 15:57 |
| Last Modified: |
16 Sep 2020 15:57 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/39457 |
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