Abstract
dc:description.abstractTraumatic brain injury (TBI) is a globally prominent form of neurological disorder, with millions of people sustaining TBI annually [1]. TBI is known to lead to both short- and long-term neurological effects, many of which occur due to functional changes in the brain after injury [2], [3]. Environmental changes within the brain after TBI are significant factors in determining functional changes and outcomes [4], [5]. It is accepted that the role of astrocytes is highly significant in the response to TBI. The objective of this study was to improve and validate a previous flux balance analysis model of astrocyte metabolism developed by Martín-Jiménez et al. to study the effects of environmental changes, specifically hypoxia and acidosis, on astrocytes following TBI [6]. To do this, updated metabolic reaction coefficients and ionic charges were incorporated to ensure stoichiometric balance across the model. Physiologically relevant constraints from experimentally derived astrocyte metabolite uptake rates bounded upper and lower limits of astrocyte metabolism. Hypoxia and acidosis were simulated by restraining extracellular oxygen uptake rate and the intracellular pH buffering capacity of astrocytes. Model results were validated against experimental analysis of oxidative phosphorylation and glycolytic genes in astrocytes. The model showed promising prediction of metabolic outcomes in hypoxic, acidosis, and combined hypoxic with acidosis conditions compared to transcriptomic analysis.
Degree
thesis:*- Name thesis:degree_name
- Master of Science
- Level thesis:degree_level
- masters
- Discipline thesis:degree_discipline
- Biomedical Engineering
- Department dc:contributor.department
- Department of Biomedical Engineering and Mechanics
- Grantor dc:publisher
- Virginia Tech
- Year dc:date.issued
- 2025
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Parker, Brian Christopher
- Chair dc:contributor.committeechair
-
- VandeVord, Pamela J.
- Committee members dc:contributor.committeemember
-
- Olsen, Michelle Lynne
- Korneva, Arina
Subjects
dc:subject × 5Rights
dc:rights- Statement dc:rights
-
- In Copyright
- Licence dc:rights.uri
- Language dc:language.iso
- en
Identifiers
dc:identifier.*- Dc Identifier Other
- vt_gsexam:43435
- OAI identifier oai:identifier
- oai:vtechworks.lib.vt.edu:10919/135406