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Dissertation
Effects of morphine and the viral protein Tat on the blood-brain barrier: implications in HIV disease and HAND
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2017
DOI:
https://doi.org/10.17918/etd-7665
Abstract
Many of the pathological observations made in human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders (HAND) have been attributed to compromise of blood-brain barrier (BBB) integrity. Certain viral proteins have been implicated in deregulation of the BBB, including the HIV-1 transactivator of transcription (Tat). Illicit drug use is also a known confounder of disease in HIV-1-infected individuals, and opioid abuse has been reported to enhance HIV-1 disease progression in multiple ways, including increased incidence and severity of HAND, as compared to non-users. In these studies, a well-characterized human brain microvascular endothelial cell line, hCMEC/D3, was utilized as an in vitro model of the BBB in order to investigate the interactions and consequences of morphine or Tat exposure on the BBB. Transport of morphine, without the production of morphine metabolites, across the hCMEC/D3 BBB was observed. In addition, changes in the expression of mRNA transcripts of tight junction proteins were seen throughout the course of hCMEC/D3 exposure to morphine. Furthermore, exposure to repeated administrations of morphine resulted in the generation of chemotactic gradients across the in vitro BBB model. When the same model was used to examine if recombinant Tat elicited a similar response, it was found that Tat did not affect general permeability of the barrier or induce MCP-1 or SDF-1 chemokine gradients. Overall, these studies demonstrate that exposure to morphine, and not Tat, results in compromise of BBB integrity by inducing alterations in molecular expression of key BBB components important to maintaining homeostatic regulation of the barrier.
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Details
- Title
- Effects of morphine and the viral protein Tat on the blood-brain barrier
- Creators
- Monique Eufemia Maubert - DU
- Contributors
- Michael R. Nonnemacher (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xviii, 202 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Microbiology and Immunology; College of Medicine; Drexel University
- Other Identifier
- 7665; 991014632444604721