Evaluating the cytotoxicity and adverse effects of diesel exhaust particle exposure on the brain’s first line of defense, the blood-brain barrier and microglia, in vitro.

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dc.contributor.advisorBruce, Erica Dawn.
dc.creatorAquino, Grace V., 1993-
dc.date.accessioned2024-07-17T13:50:08Z
dc.date.available2024-07-17T13:50:08Z
dc.date.created2023-08
dc.date.issued2023-08
dc.date.submittedAugust 2023
dc.date.updated2024-07-17T13:50:09Z
dc.description.abstractCombustion-derived particulate matter (PM) such as diesel exhaust particles (DEP) is a public health concern because chronic exposure is associated with neurodegenerative diseases (NDs) like Alzheimer’s (AD). When inhaled, fine/ultrafine DEP can travel through systemic circulation or via the olfactory bulb to the central nervous system (CNS), where it can exert adverse effects on the blood-brain barrier (BBB) and perivascular microglia. In the healthy brain, the BBB (i.e. cerebrovascular endothelial cells; ECs) and microglia function as the brain’s first line of defense, and the BBB-microglia interaction is essential in maintaining CNS health. Notably, the underlying mechanisms of PM-induced CNS disease are multifactorial and complex, rendering mechanistic inquiry in pathophysiological and toxicological studies a significant challenge. Of such mechanisms, BBB dysfunction and microglial activation are heavily implicated in NDs. While several studies have evaluated DEP exposures on BBB ECs, no study had previously evaluated DEP exposures on EC-microglia co-cultures, despite the microglia’s dual role in protection against or promotion of cerebrovascular damage and neuroinflammation. Therefore, the overall goal of this dissertation was to investigate how DEP exposure affects BBB function using cerebrovascular ECs and microglia in vitro. Chapter One (published) evaluated the effects of acute (24 hr.) DEP exposure on the cellular health, oxidative stress, and inflammation of rodent cerebrovascular ECs with and without microglia. Chapter Two (published) then evaluated the effect of acute DEP exposure on a critical, clinically- relevant drug efflux transporter (i.e. P-glycoprotein), barrier permeability, and inflammation in human immortalized cerebrovascular ECs with and without microglia. Finally, Chapter Three presents data collected using an improved, human iPSC-derived BBB model (iBMEC), and preliminary data on changes in the Amyloid-β transport system (LRP-1, RAGE, and P-gp) and in the activation state of microglia under exposure to DEP. Overall, this work is novel because it is the first to evaluate DEP’s effect on BBB-microglia co-cultures, and on the Amyloid-β transport system. Ultimately, this work improves our understanding on DEP’s adverse effects in the BBB, and highlights the potential role of PM in the etiology of AD.
dc.format.mimetypeapplication/pdf
dc.identifier.uri
dc.identifier.urihttps://hdl.handle.net/2104/12768
dc.language.isoEnglish
dc.rights.accessrightsNo access – contact librarywebmaster@baylor.edu
dc.titleEvaluating the cytotoxicity and adverse effects of diesel exhaust particle exposure on the brain’s first line of defense, the blood-brain barrier and microglia, in vitro.
dc.typeThesis
dc.type.materialtext
local.embargo.lift2025-08-01
local.embargo.terms2025-08-01
thesis.degree.departmentBaylor University. Dept. of Environmental Science.
thesis.degree.grantorBaylor University
thesis.degree.namePh.D.
thesis.degree.programEnvironmental Science
thesis.degree.schoolBaylor University

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