Neurosciences Commons^™

Exploring The Efficacy Of Mir-33 Antagonism In Promoting Regression Of Intracranial Atherosclerosis In A Nonhuman Primate Model, Peter Hecker

Theses and Dissertations--Pharmacology and Nutritional Sciences

Atherosclerosis, characterized by lipid accumulation and arterial inflammation, is a major contributor to global morbidity and mortality. Despite significant progress in understanding atherosclerosis in extracranial arteries, the study of intracranial atherosclerosis (ICAS) has been relatively neglected, despite its crucial role in stroke and vascular cognitive impairment. Challenges related to ICAS, including its location within the cranium and limited availability of suitable animal models, have hindered research progress in this area. Although nonhuman primates (NHPs) are commonly used for studying extracranial atherosclerosis, a comprehensive understanding of ICAS pathophysiology in these animals is lacking. By subjecting NHPs to a high-fat/cholesterol diet, we …

One In Every Twenty-Six, Rey'na Riggans

Capstone Showcase

There is a disorder that is rather common within the world and yet is not well known. It is a something that affects one in every twenty-six individuals. It is called epilepsy. Epilepsy is a neurological disorder in which a person to experience bursts of random electrical activity within their brains, these bursts being called "seizures." This article discusses this disorder and goes into detail about the forms of it, procedures that are done to try and help those living with epilepsy, and artwork that is inspired by this disorder.

Investigation To Examine The Profile Of Auditory Brainstem And Hearing Thresholds Using Tone Burst Audiometry Brainstem Response In A Preclinical Migraine Model, Megan Huelsing

MSU Graduate Theses

Migraine is a disabling neurological disease that is characterized by prominent auditory symptoms, including hyperacusis, which is defined as extreme sensitivity to sounds. The goal of this study was to investigate changes in hearing sensitivity and neural changes in the brainstem by measuring neural activity of the auditory brainstem in an established preclinical model of chronic migraine. To induce a chronic migraine state within the trigeminal system, male and female Sprague Dawley rats were subjected to three known human risk factors including neck muscle tension and REM sleep deprivation that promote latent sensitization, and exposure to a pungent odor, which …

Emulating Future Neurotechnology Using Magic, Jay A. Olson, Mariève Cyr, Despina Z. Artenie, Thomas Strandberg, Lars Hall, Matthew L. Tompkins, Amir Raz, Petter Johansson

Psychology Faculty Articles and Research

Recent developments in neuroscience and artificial intelligence have allowed machines to decode mental processes with growing accuracy. Neuroethicists have speculated that perfecting these technologies may result in reactions ranging from an invasion of privacy to an increase in self-understanding. Yet, evaluating these predictions is difficult given that people are poor at forecasting their reactions. To address this, we developed a paradigm using elements of performance magic to emulate future neurotechnologies. We led 59 participants to believe that a (sham) neurotechnological machine could infer their preferences, detect their errors, and reveal their deep-seated attitudes. The machine gave participants randomly assigned positive …

Monitoring Intraventricular Hemorrhage In Preterm Infants, Lilian Mn Kebaya

Electronic Thesis and Dissertation Repository

Germinal Matrix-Intraventricular hemorrhage (GMH-IVH) remains a significant cause of adverse neurodevelopmental outcomes in preterm infants. Current management options for GMH-IVH rely on serial 2-dimensional cranial ultrasound (2D cUS) ventricular measurements and clinical signs. A need exists for reliable biomarkers to aid in the early detection of posthemorrhagic ventricular dilatation (PHVD) and cerebral palsy (CP). We incorporated 3-dimensional cranial US (3D cUS) and functional infrared spectroscopy (fNIRS) to monitor ventricle volumes (VV) and spontaneous functional connectivity (sFC) in preterm infants with GMH-IVH. Infants with severe GMH-IVH who underwent cerebrospinal fluid diversion showed larger VV, which correlated with decreased sFC. Our findings …

The Use Of Kernig’S And Brudzinski’S Sign In Determining Meningitis: A Review, Crystal T. Duong, Ashton Hughes, Kerem Yilmaz

Physician Assistant Capstones, 2020-current

Objective: Assess the diagnostic value of Kernig’s and Brudzinski’s signs in determining meningitis among individuals aged 18 to 64. Design: Systematic literature review. Methods: Searches done in PubMed utilizing the terms Kernig and Brudzinski. In PubMed, studies were excluded if not in English, older than 2000 or done on animals, and meta-analyses. Results: Three studies were found including Nakao JH, et al, Thomas KE, et al, and Waghdhare S, et al. Conclusion: Kernig’s and Brudzinski’s signs have high specificity but yield a low sensitivity in determining meningitis. They are great tools to be utilized by medical providers, but only support …

Transcranial Direct Current Stimulation Of Frontal/Occipital Cortices Modulates Neural Correlates Of Cognition In Healthy Young Adults, Yasra Arif

Theses & Dissertations

An exponential rise in the use of transcranial direct current stimulation (tDCS) to modify the human brain and behavior has been observed over the last 20 years, with studies often yielding mixed outcomes. Such heterogeneity is partially attributed to the lack of a concise understanding of the underlying mechanisms. Though considered to exert modulatory effects by changing neuronal membrane polarization and synaptic efficacy, the interactive effects of offline tDCS and the neural underpinnings of cognition, both at the regional and network-level, are yet to be fully understood. Using High-Definition tDCS (HD-tDCS), Magnetoencephalography (MEG), a range of well-established cognitive paradigms, and …

Empowering Nurses To Recognize Post-Stroke Depression In The African American Community, Deidra Frisbie, Robin Simon

Doctor of Nursing Practice Projects

African Americans (AA) have the highest prevalence of stroke and death compared to other racial groups in the United States. Post-stroke depression (PSD) affects approximately 1/3 of all stroke patients and is underdiagnosed in the African American community.

Aim: By using a mHealth mobile app and a Psychiatry provider list at discharge, PSD can be identified, and interventions initiated, thus decreasing the sequela of PSD in AA.

Methods: Nurses were provided education on PSD, expressions of depression in African-Americans, cultural humility, implicit bias, and the importance of the nurse's role in developing a therapeutic relationship.

Results: Quantitative analysis revealed the …

The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland

Arts & Sciences Electronic Theses and Dissertations

The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …

Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan

Arts & Sciences Electronic Theses and Dissertations

The survival of a species is inextricably linked to its ability to successfully navigate and interact with its surroundings, whether to seek safety from predators or gain sustenance from prey. Both functions are performed by mice, guided by vision, and rely on intricate processing in the retina and subcortical targets in the brain. This dissertation addresses how specific features of the visual environment and specific retinal ganglion cell circuits that sample a particular space in the visual environment are used to guide efficient predation in mice.Recent studies have begun to link the ability to detect, track, and ultimately capture prey …

Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones

Arts & Sciences Electronic Theses and Dissertations

K+ homeostasis is important for maintaining healthy, physiological levels of neuronal activity. Glial cells play a central role in maintaining homeostatic ion gradients. In previous work from our lab, we unravel a glial K+ buffering program that is centered on a key kinase, salt-inducible kinase 3 (SIK3). SIK3-HDAC4 signaling in glial regulates the transcription of channels and transporters involved in water and ion transport. Defects in this pathway lead to peripheral nerve edema, neuronal hyperactivity, and seizure sensitivity. In an hyperexcitability mutant, eag Shaker, we show this pathway is downregulated and genetic activation suppresses seizure behavior. In this thesis, I …

The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan

Arts & Sciences Electronic Theses and Dissertations

The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …

Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard

Arts & Sciences Electronic Theses and Dissertations

The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …

Rna Editing Of Microtubule-Associated Protein Tau Circular Rnas Promotes Their Translation And Tau Tangle Formation, Justin Ralph Welden, Giorgi Margvelani, Karol Andrea Arizaca Maquera, Bhavani Gudlavalleti, Sandra C. Miranda Sardón, Alexandre Rosa Campos, Noémie Robil, Daniel C. Lee, Alvaro G. Hernandez, Wang-Xia Wang, Jing Di, Pierre De La Grange, Peter T. Nelson, Stefan Stamm

Sanders-Brown Center on Aging Faculty Publications

Aggregation of the microtubule-associated protein tau characterizes tauopathies, including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-Tau). Gene expression regulation of tau is complex and incompletely understood. Here we report that the human tau gene (MAPT) generates two circular RNAs (circRNAs) through backsplicing of exon 12 to either exon 7 (12→7 circRNA) or exon 10 (12→10 circRNA). Both circRNAs lack stop codons. The 12→7 circRNA contains one start codon and is translated in a rolling circle, generating a protein consisting of multimers of the microtubule-binding repeats R1–R4. For the 12→10 circRNA, a start codon can be introduced by two …

Genetic Expression Changes And Pathologic Findings Associated With Hyperhomocysteinemia In Human Autopsy Brain Tissue, Erica M. Weekman, Zachary Winder, Colin B. Rogers, Erin L. Abner, Tiffany L. Sudduth, Ela Patel, Adam J. Dugan, Shuling X. Fister, Brandi Wasek, Peter T. Nelson, Gregory A. Jicha, Teodoro Bottiglieri, David W. Fardo, Donna M. Wilcock

Sanders-Brown Center on Aging Faculty Publications

Introduction: Vascular contributions to cognitive impairment and dementia (VCID) are a leading cause of dementia. An underappreciated, modifiable risk factor for VCID is hyperhomocysteinemia (HHcy), defined by elevated levels of plasma homocysteine, most often due to impaired B vitamin absorption in aged persons. Studies aimed at identifying neuropathologic features and gene expression profiles associated with HHcy have been lacking.

Methods: A subset of research volunteers from the University of Kentucky Alzheimer’s Disease Research Center longitudinal cohort came to autopsy and had ante mortem plasma homocysteine levels available. Brain tissue and blood plasma drawn closest to death were used to measure …

Nursing Considerations For Post-Traumatic Amnesia After A Traumatic Brain Injury, Hannah Grant

Senior Honors Theses

A period known as post-traumatic amnesia (PTA) often follows a traumatic brain injury (TBI). PTA is characterized by anterograde and retrograde amnesia, confusion, disorientation, and agitation. The duration and severity of PTA is a key indicator of the long-term prognosis after a TBI, so proper assessment and nursing care of a PTA patient is crucial. TBIs range from mild to severe, but primarily affect the fronto-temporal lobes. In PTA, both neural lesions and white matter damage within the parahippocampal region can cause PTA. A nurse must perform a thorough assessment of a TBI patient, but, since PTA is a key …

Data-Driven Neuroanatomical Subtypes In Various Stages Of Schizophrenia: Linking Cortical Thickness, Glutamate, And Language Functioning, Liangbing Liang

Electronic Thesis and Dissertation Repository

The considerable variation in the spatial distribution of cortical thickness changes has been used to parse heterogeneity in schizophrenia. We aimed to recover a ‘cortical impoverishment’ subgroup with widespread cortical thinning. We applied hierarchical cluster analysis to cortical thickness data of three datasets in different stages of psychosis and studied the cognitive, functional, neurochemical, language and symptom profiles of the observed subgroups. Our consensus-based clustering procedure consistently produced a subgroup characterized by significantly lower cortical thickness. This ‘cortical impoverishment’ subgroup was associated with a higher symptom burden in a clinically stable sample and higher glutamate levels with language impairments in …

Apoe Genetics Influence Murine Gut Microbiome, Diana J. Zajac, Stefan J. Green, Lance A. Johnson, Steven Estus

Sanders-Brown Center on Aging Faculty Publications

Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we evaluated effects of APOE heterozygosity and tested whether these overall results extended to mice maintained under ideal conditions for microbiome analyses. To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, homozygous APOE3 mice were crossed to homozygous APOE2 or homozygous APOE4 mice prior to the study, and the resulting …

Single Low-Dose Targeted Bevacizumab Infusion In Adult Patients With Steroid-Refractory Radiation Necrosis Of The Brain: A Phase Ii Open-Label Prospective Clinical Trial, Shervin R. Dashti, Robert J. Kadner, Bradley S. Folley, Jason P. Sheehan, Dong Y. Han, Richard J. Kryscio, Mary B. Carter, Lisa B. E. Shields, Brian M. Plato, Renato V. La Rocca, Aaron C. Spalding, Tom L. Yao, Justin F. Fraser

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVE There is an unmet need for safe and rapidly effective therapies for refractory brain radiation necrosis (RN). The aim of this prospective single-arm phase II trial was to evaluate the safety and efficacy of a single low-dose targeted bevacizumab infusion after blood-brain barrier disruption (BBBD) in adult patients with steroid-refractory brain RN.

METHODS Ten adults with steroid-refractory, imaging-confirmed brain RN were enrolled between November 2016 and January 2018 and followed for 12 months after treatment. Bevacizumab 2.5 mg/kg was administered as a one-time targeted intra-arterial infusion immediately after BBBD. Primary outcomes included safety and > 25% decrease in lesion volume. …

Sex Differences In The Disease Progression Of Ftd Vs Ad, Abigail Mitchell, Danielle Frances, Chase Metzger

Science University Research Symposium (SURS)

Abigail Mitchell, Danielle Frances, Chase Metzger

Sex Differences in the Disease Progression of FTD vs AD.

Abstract

Neurodegenerative diseases are on the rise in aging populations due to the upper tier of the population getting larger in that age group (Zheng & Chen, 2022). Knowing this, there is great benefit in more accurate and early diagnosis of conditions like frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Particularly, it is important to understand which variables may contribute to differences in disease burden and progression of associated sequalae, with one of those variables being biological sex. The current study investigated sex differences …