Oluwagbemisola Aderibigbe
BME PhD Defense Presentation

Date: 2025-11-03
Time: 9:30 AM - 11:30 AM
Location / Meeting Link: MoSE Room 3201A / https://emory.zoom.us/j/92257778072

Committee Members:
Susan S. Margulies, PhD (Advisor) Levi B. Wood, PhD (Co-Advisor) Michelle C. LaPlaca, PhD Erin M. Buckley, PhD Manu O. Platt, PhD Christopher C. Giza, MD


Title: Molecular and Pathological Signatures of Time and Cyclosporine A Induced Neuroprotection Following Traumatic Brain Injury in Infants and Juveniles

Abstract:
Mild traumatic brain injury (mTBI) is a leading cause of morbidity in children. It can cause poor short- and long-term neurological, cognitive, cerebrovascular, and emotional deficits that can affect every aspect of a child’s life. Additionally, mTBI is highly heterogeneous and presents with different patterns of injury, severity, and outcomes. Despite decades of clinical and pre-clinical research, there is still limited holistic understanding of the molecular changes driving both acute and persisting pathophysiological hallmarks following pediatric mTBI. The factors contributing to heterogeneity are also poorly understood, and there are currently no available treatments to improve outcomes in pediatric patients. Designing targeted novel therapeutics and measures for mTBI and gaining knowledge of molecules and how they are modulated is crucial. To advance our knowledge, by using a sagittal rapid non-impact head rotation (RNR) piglet mTBI model, we examined transcriptional profiles (mRNA and miRNAs) and pathological changes at multiple timepoints, brain regions, rotational severities, and ages following mTBI. Additionally, we evaluated the role of a drug, Cyclosporine A, in modulating transcriptional profiles to drive neuroprotection. Overall, by utilizing bulk RNA-sequencing and an RNR piglet mTBI model, this dissertation, 1) identified key molecular signatures (mRNA and miRNAs) altered at two timepoints and brain regions following mTBI, 2) elucidated the role of a 20 mg/kg/day Cyclosporine A (CsA) treatment in accelerating neuronal recovery signatures, and 3) highlighted distinct molecular alterations between two pediatric age groups (newborn vs. juvenile) and two rotational loads (low vs high RNR) following mTBI. Taken together, we uncovered key repair and recovery associated molecules that hold promise as gene therapy targets and highlighted the role of CsA in driving neuronal recovery following pediatric mTBI.