Graduation Year
2024
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Medical Sciences
Major Professor
Travis Jackson, Ph.D.
Committee Member
Paula Bickford, Ph.D.
Committee Member
David Lominadze, Ph.D.
Committee Member
Kevin Nash, Ph.D.
Keywords
Traumatic Brain Injury, Ischemia, RBM5, Sex Differences, Neuronal Culture
Abstract
Traumatic brain injury (TBI) is a worldwide health burden that causes death and disability. Clinical management of TBI involves guideline-based protocols to limit secondary brain injury but there remains an unmet need for therapeutics to target neuroprotection and to improve cognitive outcomes in patients. This dissertation concerns the examination of RNA binding motif 5 (RBM5) as a potential therapeutic gene target to promote neuroprotection in models of TBI. RBM5 is a potent pro-death tumor suppressor gene in cancer. We hypothesized that it also promotes cell death in neurons in the brain and therefore its inhibition would decrease neuropathology following CNS trauma. Studies were carried out using novel conditional RBM5 knockout (KO) mice. This transgenic tool allowed us to selectively inhibit RBM5 in the brain in intact animals, and to inhibit RBM5 in primary neurons in culture. We discovered that endogenous RBM5 levels are decreased in the injured male brain and in isolated injured male neurons in culture. Also, our work shows that inhibition of RBM5 in the brain did not alter hippocampal neuronal survival in the in vivo controlled cortical impact (CCI) model of TBI at 7d post-injury, nor did it affect cell survival 24h post-injury in cortical neurons in the in vitro mechanical stretch injury model of trauma. Nor was RBM5 KO neuroprotective in the in vitro oxygen glucose deprivation (OGD) model of ischemia. However, we elucidated novel sex differences with respect to RBM5 KO dependent changes on cell signaling pathways in TBI injured males versus females. Additional studies are warranted to determine if RBM5 downregulation disrupts CNS recovery in injured males and to further elucidate the role of RBM5 in brain function.
Scholar Commons Citation
Snyder, Kara L., "Elucidating the role of the tumor suppressor gene RNA-binding motif 5 (RBM5) in models of traumatic brain injury" (2024). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/10246
