Mitochondria, Inflammation, and T-Cell Metabolism in a Rat Model of Pediatric Mild Traumatic Brain Injury
| dc.contributor.advisor | Esser, Michael J. | |
| dc.contributor.advisor | Shutt, Timothy E. | |
| dc.contributor.author | Fraunberger, Erik Albert | |
| dc.contributor.committeemember | Gallagher, Clare N. | |
| dc.contributor.committeemember | Yeates, Keith Owen | |
| dc.contributor.committeemember | Kurrasch, Deborah M. | |
| dc.contributor.committeemember | Noble-Haeusslein, Linda J. | |
| dc.date | 2020-11 | |
| dc.date.accessioned | 2020-07-28T21:53:37Z | |
| dc.date.available | 2020-07-28T21:53:37Z | |
| dc.date.issued | 2020-07-24 | |
| dc.description.abstract | Representing approximately 20,000 emergency department visits in Canada every year, pediatric traumatic brain injury (TBI) can be an intractable medical problem with limited treatment options. While most research has been directed towards the devastating, moderate-severe end of the TBI spectrum, most clinical injuries present as mild with minimal duration of loss of consciousness and lack of macroscopic damage to neural tissue. The pediatric population is especially vulnerable to the consequences of these milder injuries as developmental processes and long-term functioning can be impacted by negative cognitive and emotional changes persisting for up to and beyond one month after injury. Although we have some understanding of TBI pathophysiology including diffuse axonal injury, mitochondrial dysfunction, and cerebral blood flow dysregulation, there is still no clear understanding as to how the developing brains responds and adapts to injury. This thesis takes up the challenge of studying a mild, heterogeneous injury using a juvenile rat TBI model. It begins to unravel some of the complex pathophysiological patterns after pediatric mTBI from the perspectives of mitochondrial function, inflammation, and T-cell metabolism. First, we documented females having greater mitochondrial oxygen consumption in brain cells 21 days after a single mTBI, offering insight into one mechanism for persistent impairments in females following pediatric mTBI. Second, we highlight inflammatory changes to the understudied cerebellum, show cytokines as poor biomarkers of mTBI, and illustrate dynamic changes in inflammation after pediatric mTBI using network analysis. Third, we found preliminary evidence of metabolic changes in CD4+ T-cells starting at 24h post-mTBI, revealing possible upstream changes to observed inflammation previously shown only at 4-7 days after injury. Seeing changes in substrate oxidation patterns presaging inflammation may reveal nascent benefits to targeting metabolism to alter inflammation for therapeutic intervention. Collectively, the work in this thesis significantly advances our knowledge of pediatric mTBI pathophysiology, introduces new ways to interpret inflammation data, and paves the way for the investigation of novel pathways for therapeutic intervention. | en_US |
| dc.identifier.citation | Fraunberger, E. A. (2020). Mitochondria, Inflammation, and T-Cell Metabolism in a Rat Model of Pediatric Mild Traumatic Brain Injury (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. | en_US |
| dc.identifier.doi | http://dx.doi.org/10.11575/PRISM/38045 | |
| dc.identifier.uri | http://hdl.handle.net/1880/112342 | |
| dc.language.iso | eng | en_US |
| dc.publisher.faculty | Cumming School of Medicine | en_US |
| dc.publisher.institution | University of Calgary | en |
| dc.rights | University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission. | en_US |
| dc.subject.classification | Neuroscience | en_US |
| dc.title | Mitochondria, Inflammation, and T-Cell Metabolism in a Rat Model of Pediatric Mild Traumatic Brain Injury | en_US |
| dc.type | doctoral thesis | en_US |
| thesis.degree.discipline | Medicine – Neuroscience | en_US |
| thesis.degree.grantor | University of Calgary | en_US |
| thesis.degree.name | Doctor of Philosophy (PhD) | en_US |
| ucalgary.item.requestcopy | true | en_US |