Pharmacology, Toxicology and Environmental Health Commons^™

Neuroinflammatory And Metabolomic Temporal Dynamics From Inhaled Wildfire Smoke With Attenuation Via Pharmacological Intervention, David Scieszka, David Scieszka

Biomedical Sciences ETDs

Wildfire smoke is a global issue affecting nearly all humans on the surface of this Earth. Smoke dispersion from wildfires can span continents and cross oceans with amazing ease. Furthermore, total acres of land burned per year in the United States has roughly doubled since 1980, meaning this issue will persist for an indeterminate amount of time. Exposure to wildfire smoke is hazardous and promotes aging-associated events in the cardiopulmonary systems. Yet long- and short-term effects on the brain remain relatively unknown. From these, it is critically important to understand the neurological impacts from wildfire smoke exposure; to compare these …

Novel Therapeutic Strategies For Alzheimer’S Disease: Prostaglandin D2 Signaling And Its Human Polymorphisms As Well As A Polypharmacological Approach, Charles H. Wallace

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is an age related neurodegenerative disease with pathology that includes amyloid plaques, neurofibrillary tangles and non-resolving neuroinflammation. Non-resolving neuroinflammation lasts the entire course of the disease and has deleterious effects and is often thought to accelerate AD pathology. Non-Steroidal Anti-inflammatory Drugs (NSAIDs) have commonly been used as therapeutics to treat pain, inflammation and vascular. NSAIDs work by altering the cyclooxygenase (COX) mediated biosynthesis of prostaglandins which are lipid mediators that have many physiological functions, for example nociception, inflammation and vasodilation. Epidemiological studies support the notion that NSAIDs could be used to treat AD. Yet, clinical trials using …

Behavioral Effects And Neurobiological Mechanisms Of 3-Aminobenzimide In A Rodent Model Of Chronic Psychological Stress, Liza Wills

Electronic Theses and Dissertations

Major depressive disorder (MDD) is a leading cause of disability worldwide, with a lifetime prevalence rate of approximately 20%. Inadequate pharmacological treatment methods for MDD are a significant debilitating factor. Patient estimates suggest that the treatment resistance rate for pharmacological interventions is over 30%. Postmortem analyses of human tissue of individuals diagnosed with MDD have shown an increase in Poly (ADP-ribose) polymerase 1 (PARP-1) mRNA gene expression in prefrontal cortical white matter when compared to psychiatrically normal brain tissue. In order to further investigate this issue, the present study used the social defeat stress/chronic unpredictable stress (SDS + CUS) rodent …

N, N-Dimethylacetamide Targets Neuroinflammation In Alzheimer’S Disease In In Vitro And Ex Vivo Models, Zenghui Wei

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disorder with no cure, accounting for 60-80% of cases of dementia. While the two pathologic hallmarks of AD, senile plaques from extracellular deposition of amyloid β-protein (Aβ) and tau-based neurofibrillary tangles (NFT), have been known for decades, the pathogenesis of AD remains unclear. In recent years, anti-neuroinflammatory treatment has entered the spotlight in AD research. In previous studies, we have shown that N,N-dimethylacetamide (DMA), a common drug excipient, is a potent anti-inflammatory agent. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

Role Of Mcp-1 And Ccr2 In Ethanol-Induced Damage In The Developing Brain, Kai Zhang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Fetal alcohol spectrum disorders (FASD) are caused by alcohol exposure during pregnancy and is the leading cause of mental retardation. Alcohol exposure during development results in the loss of neurons in the developing brain. The underlying molecular mechanisms are unclear and there currently is no cure for FASD. Ethanol-induced neuronal death is accompanied by neuroinflammation. Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. Using a third trimester equivalent mouse model of ethanol exposure, we found that treatment of Bindarit (MCP-1 synthesis inhibitor) and RS504393 (CCR2 …

Flavonoids With Novel Nicotinic Activity As Potential Pharmacotherapies To Treat Ethanol-Induced Neurotoxicity, Joseph A. Lutz

Theses and Dissertations--Pharmacy

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, …

Bioaccumulation And Neuroinflammation Of Gold Nanoparticles In The Central Nervous System, Fahimeh Fallahi

Browse all Theses and Dissertations

Gold nanoparticles (GNPs) possess unique physicochemical properties that may facilitate entry into the central nervous system (CNS) where they may act therapeutically. There is little information on biodistribution or inflammatory effects of GNPs in specific brain regions. Brain Localization and neuroinflammatory response to citrate-capped spherical GNP (10 nm) was determined 24 hours after intravenous (IV) injection in male C57Bl mice. A known inflammogen, lipopolysaccharide (LPS, 2 mg kg-1, SC), was tested as a positive control supplement. Aggregation of GNPs was measured using various Phosphate-Buffered Saline (PBS) concentrations (10, 1, 0.1, 0.01 X) to determine the optimal buffer concentration to maintain …

Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang

Legacy Theses & Dissertations (2009 - 2024)

Autism is a neurodevelopmental disorder with unknown etiology, affecting about 1 in 110 children in the US. Here, we show that developmental exposure to anti-brain Abs impaired mouse social behaviors. BTBR mice, a mouse strain with high serum anti-brain Abs and behaviors that resemble autism, have more activated splenic B cells, CD4+ T cells (Th1, Th2 and Th17 subsets), and CD4+ T cells with expression of Vb6 chains than B6 mice (the control H-2 identical strain). Elevated numbers of activated (CD25+) CD4+Vb6+ cells also were detected in thymic preparations. All of the immunological and behavioral parameters of BTBR mice were …

Neurodegeneration And Neuroinflammation In A Mouse Model Of Sarin Exposure, Molly Elizabeth Davidson

Browse all Theses and Dissertations

Sarin is an organophosphorus (OP) ester chemical warfare agent (CWA) that has been used in past terrorist attacks. It remains a threat today because of its ease of manufacture and dispersal. Sarin acts by irreversibly inactivating acetylcholinesterase and interfering with neurotransmission by allowing acetylcholine to build up at neuro-effector junctions, where it continuously elicits a response. Symptoms of sarin toxicity include seizures, hypersecretions, respiratory distress and death in extreme cases. Previous studies on OP poisoning indicate that sarin exposure causes neurodegeneration and neuroinflammation in conjunction with seizure activity. In order to determine the mode of neuronal death and the extent …