Dissertation Defense Schedule
Academic Excellence
Sharing original dissertation research is a principle to which the University of Delaware is deeply committed. It is the single most important assignment our graduate students undertake and upon completion is met with great pride.
We invite you to celebrate this milestone by attending their dissertation defense. Please review the upcoming dissertation defense schedule below and join us!
PROGRAM | Chemical Engineering
Development and Application of an In Vitro Blood-Brain Barrier Model to Investigate Intravenous Immunoglobulin Therapy for Alzheimer’s Disease
By: Diane Wuest Chair: Kelvin Lee
ABSTRACT
One of the largest and fastest growing sectors in the global pharmaceutical industry is the development of treatments for diseases of the central nervous system. Unfortunately, current systemically administered medications do not achieve optimum therapeutic efficacy in the brain due to limitations in crossing the blood-brain barrier (BBB). Further research is needed to enhance the understanding of how and what molecules can pass through the BBB, and the creation of an in vitro BBB model is crucial to study the cellular constituents and the dynamic capabilities of the BBB that are difficult or nearly impossible to resolve in vivo. The most prevalent BBB model consists of a monolayer of endothelial cells grown on a porous membrane submerged in the wells of a multi-well plate. The large range of cell types available, cell culture variable set points (species, generation, co-culture setup), and system variable set points (membrane configuration, media composition) has resulted in an expansive number of unique models in the field. The significance of our work lies in presenting an in vitro BBB model based on a rational understanding of model configurations and applicability for advancing brain therapeutic research. The first objective of this research was to construct an optimal in vitro BBB model by statistically screening model parameter set points using primary and immortalized murine endothelial cells and astrocytes. Two sets of sequential screening experiments identified optimal cell culture growth parameter set points and an optimal membrane configuration, which increased model performance 4-fold. The second objective of our work applied this optimized model to investigate BBB phenomena occurring in Alzheimer’s disease (AD) and its treatment with intravenous immunoglobulin (IVIG) therapy, a passive immunotherapeutic under investigation for AD in human clinical trials. We quantified IVIG transport into the brain in the presence of Aβ peptides and assessed the subsequent effects on decreasing inflammation. IVIG accumulated in the brain side at physiologically relevant levels and was found to decrease inflammation when low Aβ levels were present. In conclusion, the optimized in vitro BBB model is a valuable tool for efficiently advancing the study of brain diseases and their potential therapeutics.
The Process
Step-by-Step
Visit our “Step-by-Step Graduation Guide” to take you through the graduation process.From formatting your Dissertation to Doctoral Hooding procedures.
Dissertation Manual
Wondering how to set up the format for your paper. Refer to the “UD Thesis/Dissertation Manual” for formatting requirements and more.
Defense Submission Form
This form must be completed two weeks in advance of a dissertation defense to meet the University of Delaware Graduate and Professional Education’s requirements.
