Theses

Date of Award

2025

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biological Sciences

First Advisor

Dr. Pratyusha Mandal

Second Advisor

Dr. Stephen Redenti

Third Advisor

Dr. Julio Gallego-Delgado

Abstract

Acute diabetes characterized by high spikes in blood glucose levels in association with severe hyperglycemia can lead to an increased risk of ischemic stroke in the brain. To better understand high blood glucose levels, hyperglycemia, in the brain we explored its effects on endothelial cells. Endothelial cells line the inner walls of blood vessels and are directly impacted in hyperglycemia. Brain endothelial cells are a major component of the blood brain barrier (BBB) which tightly regulates the brain’s microenvironment. The type of cell death such as apoptosis, caspase dependent, or necroptosis, caspase independent, can exacerbate diabetes associated complications. There is an urgent need to characterize and understand the mechanism of death that brain endothelial cells undergo in a hyperglycemic condition. To study endothelial dysfunction in barrier systems such as the blood brain barrier (BBB) we conducted in vitro experiments on Human Brain Microvascular Endothelial Cells (HBMECs) in a hyperglycemic condition when caspases are inhibited. Our study characterizes the morphological, and the cell death and cell stress pathways brain endothelial cells undergo in hyperglycemia when pan-caspase function is impaired. We discovered that these cells, when pan-caspases are inhibited, are capable of undergoing a necroptosis-like cell death pathway and have increased tight junction expression. Our research provides valuable insights into caspase function and necroptosis in brain endothelial cells in hyperglycemic conditions.

Available for download on Saturday, May 30, 2026

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