Neurosciences Commons^™

Novel Murine Glioblastoma Models That Reflect The Immunotherapy Resistance Profile Of A Human Disease, Chao-Hsien Chen, Renee L Chin, Genevieve P Hartley, Spencer T Lea, Brian J Engel, Cheng-En Hsieh, Rishika Prasad, Jason Roszik, Takashi Shingu, Gregory A Lizee, Amy B Heimberger, Steven W Millward, Jian Hu, David S Hong, Michael A Curran

Faculty, Staff and Student Publications

BACKGROUND: The lack of murine glioblastoma models that mimic the immunobiology of human disease has impeded basic and translational immunology research. We, therefore, developed murine glioblastoma stem cell lines derived from Nestin-CreERT2QkL/L; Trp53L/L; PtenL/L (QPP) mice driven by clinically relevant genetic mutations common in human glioblastoma. This study aims to determine the immune sensitivities of these QPP lines in immunocompetent hosts and their underlying mechanisms.

METHODS: The differential responsiveness of QPP lines was assessed in the brain and flank in untreated, anti-PD-1, or anti-CTLA-4 treated mice. The impact of genomic landscape on the responsiveness of each tumor was measured through …

Piezo2 In Somatosensory Neurons Controls Gastrointestinal Transit, M Rocio Servin-Vences, Ruby M Lam, Alize Koolen, Yu Wang, Dimah N Saade, Meaghan Loud, Halil Kacmaz, Suzanne Frausto, Yunxiao Zhang, Arthur Beyder, Kara L Marshall, Carsten G Bönnemann, Alexander T Chesler, Ardem Patapoutian

Duncan NRI Faculty and Staff Publications

The gastrointestinal tract is in a state of constant motion. These movements are tightly regulated by the presence of food and help digestion by mechanically breaking down and propelling gut content. Mechanical sensing in the gut is thought to be essential for regulating motility; however, the identity of the neuronal populations, the molecules involved, and the functional consequences of this sensation are unknown. Here, we show that humans lacking PIEZO2 exhibit impaired bowel sensation and motility. Piezo2 in mouse dorsal root, but not nodose ganglia is required to sense gut content, and this activity slows down food transit rates in …

The Role Of Occupational Therapy In Duchenne Muscular Dystrophy, Mina Salinas, Mary Greer, Rudy Seward

Summer 2023 Virtual OTD Capstone Symposium

Duchenne muscular dystrophy (DMD) is a progressive inherited type of muscular dystrophy that results in progressive muscle weakness and requires a multidisciplinary approach for disease management. Occupational Therapy (OT) services are extremely valuable to this population as individuals diagnosed with this condition face significant difficulty in areas of occupational performance. Research shows occupational therapy services are not being received consistently and there are disparities in services received leaving a gap in the literature about the referral process and the understanding of OT's role.

An Sms Text Message-Based Type 2 Diabetes Prevention Program For Hispanic Adolescents With Obesity: Qualitative Co-Design Process, Erica Soltero, Callie Lopez, Sandra Mihail, Ayleen Hernandez, Salma M Musaad, Teresia M O'Connor, Debbe Thompson

Faculty, Staff and Students Publications

BACKGROUND: SMS text message-based interventions are a promising approach for reaching and engaging high-risk youths, such as Hispanic adolescents with obesity, in health promotion and disease prevention opportunities. This is particularly relevant, given that SMS text messaging is widely accessible and available and that adolescents are frequent texters. Including youths in the development of SMS text message content can lead to more acceptable and relevant messaging; however, few studies include this group as cocollaborators.

OBJECTIVE: This study aimed to use a co-design process to inform the development of SMS text messages that promote healthy physical activity (PA) and sleep behaviors …

Injury Induced Neuroplasticity And Cell Specific Targeting Of The Lumbar Enlargement For Gene Therapy., Brandon Lee Brown

Electronic Theses and Dissertations

This dissertation is an examination of spinal cord injury induced neuroplasticity and tests whether noninvasive gene therapy can successfully target neurons in the lumbar spinal cord. It begins with an overview of neural control of locomotion and a brief summary of therapeutics that are used and/or in development for treating spinal anatomically characterize s subset of neurons in the spinal cord, long ascending propriospinal neurons, that are involved in interlimb coordination. Characterization of these neurons allows for subsequent evaluation of their potential involvement in injury induced neuroplasticity. This dissertation is divided into five chapters, covering spinal cord injury and therapeutics. …

A Comparison Of Pm-Nato3’S Influence On Neural Progenitors And Mature Dopamine Neurons, Mary E. West

Masters Theses

This thesis presents significant findings regarding the role of PM-Nato3 in its interaction with developing neurons in the context of Parkinson's disease (PD) and regenerative medicine. We investigated the effects of PM-Nato3 on dopamine (DA) neurogenesis under different culture conditions, both in vitro and in vivo. In the standard dopaminergic culture condition, PM-Nato3 potentially increased the speed of DA neuron production but did not significantly increase the yield of DA neurons. In a minimal culture condition, there was no notable difference between the control and PM-Nato3 conditions, suggesting minimal impact on DA neurogenesis. In vivo studies using a mouse model …

The Genetic Relationship Between Peripheral Inflammation And Alzheimer’S Disease, Davis Cammann

UNLV Theses, Dissertations, Professional Papers, and Capstones

Alzheimer’s disease (AD) is the leading cause of dementia worldwide, and has become an ever-present problem in aging populations. An increasing body of evidence suggests that neuroinflammation is one of the key drivers of AD pathology. One overlooked contributor to this burden is peripheral inflammation throughout the body. Due to increased permeability of the blood-brain-barrier (BBB) in older age, inflammatory plasma proteins and immune cells infiltrate the CNS and drive neuroinflammation through interactions with neurons and glia. In addition, age-related changes in the composition of gut microbiome taxa lead to increased gut permeability and inflammatory burden. Because inflammatory factors are …

Sculpting Astrocyte Diversity Through Circuits And Transcription, Yi-Ting Cheng, Junsung Woo, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes are the most abundant glial cell in the central nervous system and occupy a wide range of roles that are essential for brain function. Over the past few years, evidence has emerged that astrocytes exhibit cellular and molecular heterogeneity, raising the possibility that subsets of astrocytes are functionally distinct and that transcriptional mechanisms are involved in encoding this prospective diversity. In this review, we focus on three emerging areas of astrocyte biology: region-specific circuit regulation, molecular diversity, and transcriptional regulation. This review highlights our nascent understanding of how molecular diversity is converted to functional diversity of astrocytes through the …

Robotic Surgery And Hospital Reimbursement, Nicholas H Yim, Jacob Mccarter, Tareck Haykal, Ali M Aral, Jessie Z Yu, Edward Reece, Sebastian Winocour

Faculty, Staff and Students Publications

The field of plastic surgery remains at the forefront of technological and surgical innovation. However, the promising applications of robotics in plastic surgery must be thoughtfully balanced with hospital finances and reimbursements. Robotic systems have been studied extensively across multiple surgical disciplines and across diverse health care systems. The results show that there may be equal or better patient outcomes than alternatives. In an era where fiscal responsibility in health care is a top priority, thoughtful budgeting and spending must be considered and revisited frequently to attain sustainable organizational models that ensure appropriate use of robotic technology.

Epileptic Seizure Classification Using Image-Based Data Representation, Amber Surles

Graduate Theses and Dissertations (2019 - present)

Epilepsy is a recurrence of seizures caused by a disorder of the brain in over 3.4 million people nationwide. Some people are able to predict their seizures based off prodrome, which is an early sign or symptom that usually resembles mood changes or a euphoric feeling even days to an hour before occurrence. Consequently, the natural instincts of the body to react to an upcoming attack lends credence to the existence of a pre-ictal state that precedes seizure episodes. Physicians and researchers have thus sought for an automated approach for predicting or detecting seizures.

In this research, we evaluate the …

Primary Balloon Angioplasty Of Venous Sinus Stenosis In Idiopathic Intracranial Hypertension, Juan Carlos Martinez-Gutierrez, Matthew J Kole, Victor Lopez-Rivera, Mehmet Enes Inam, Rosa Tang, Nagham Al-Zubidi, Ore-Ofeoluwatomi Adesina, Elvira Lekka, Allison C Engstrom, Sunil Sheth, Claudia Pedroza, Arthur L Day, Peng Roc Chen

Faculty, Staff and Student Publications

Background: Venous sinus stenosis (VSS) stenting has emerged as an effective treatment for patients with Idiopathic Intracranial Hypertension (IIH). However, stenting carries risk of in-stent stenosis/thrombosis and cumulative bleeding risk from long-term dual antiplatelet (DAPT) use. Thus, we investigated the potential safety and efficacy of primary balloon angioplasty as an alternative to stenting in IIH.

Methods: A prospectively maintained single-center registry of IIH patients undergoing endovascular procedures was queried. Inclusion criteria included patients with confirmed IIH and angiographically demonstrable VSS who underwent interventions from 2012- 2021. Patients were dichotomized into primary balloon angioplasty (Group A) and primary stenting (Group S), …

Eosinophils Promote Effector Functions Of Lung Group 2 Innate Lymphoid Cells In Allergic Airway Inflammation In Mice, William E Lesuer, Melanie Kienzl, Sergei I Ochkur, Rudolf Schicho, Alfred D Doyle, Benjamin L Wright, Matthew A Rank, Alexander S Krupnick, Hirohito Kita, Elizabeth A Jacobsen

Faculty, Staff and Student Publications

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are critical mediators of type 2 respiratory inflammation, releasing IL-5 and IL-13 and promoting the pulmonary eosinophilia associated with allergen provocation. Although ILC2s have been shown to promote eosinophil activities, the role of eosinophils in group 2 innate lymphoid cell (ILC2) responses is less well defined.

OBJECTIVE: We sought to investigate the role of eosinophils in activation of ILC2s in models of allergic asthma and in vitro.

METHODS: Inducible eosinophil-deficient mice were exposed to allergic respiratory inflammation models of asthma, such as ovalbumin or house dust mite challenge, or to innate models of …

Neuro-Immune Interactions And Immuno-Oncology, Narmina Khanmammadova, Shajedul Islam, Padmanee Sharma, Moran Amit

Faculty, Staff and Student Publications

The nervous system is an important component of the tumor microenvironment (TME), driving tumorigenesis and tumor progression. Neuronal cues (e.g., neurotransmitters and neuropeptides) in the TME cause phenotypic changes in immune cells, such as increased exhaustion and inhibition of effector cells, which promote immune evasion and cancer progression. Two types of immune regulation by tumor-associated nerves are discussed in this review: regulation via neuronal stimuli (i.e., by neural transmission) and checkpoint-mediated neuronal immune regulation. The latter occurs via the expression of immune checkpoints on the membranes of intratumoral nerves and glial cells. Here, we summarize novel findings regarding the neuroimmune …

Combining Voltage-Sensitive Dye, Carbon Fiber Array, And Extracellular Nerve Electrodes Using A 3-D Printed Recording Chamber And Manipulators, Curtis L Neveu, Yu Huan, Yuto Momohara, Paras R Patel, Hillel J Chiel, Cynthia A Chestek, John H Byrne

Faculty, Staff and Student Publications

BACKGROUND: The analyses of neuronal circuits require high-throughput technologies for stimulating and recording many neurons simultaneously with single-neuron precision. Voltage-sensitive dyes (VSDs) have enabled the monitoring of membrane potentials of many (10-100 s) neurons simultaneously. Carbon fiber electrode (CFE) arrays allow for stimulation and recording of many neurons simultaneously, including intracellularly.

NEW METHOD: Combining CFE with VSD leverages the advantages of both technologies, allowing for stimulation of single neurons while recording the activity of the entire network. 3-D printing technology was used to develop a chamber to simultaneously perform VSD imaging, CFE array recording, and extracellular recording from individual glass …

Cerebellar Dysfunction As A Source Of Dystonic Phenotypes In Mice, Amanda M Brown, Meike E Van Der Heijden, H A Jinnah, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

There is now a substantial amount of compelling evidence demonstrating that the cerebellum may be a central locus in dystonia pathogenesis. Studies using spontaneous genetic mutations in rats and mice, engineered genetic alleles in mice, shRNA knockdown in mice, and conditional genetic silencing of fast neurotransmission in mice have all uncovered a common set of behavioral and electrophysiological defects that point to cerebellar cortical and cerebellar nuclei dysfunction as a source of dystonic phenotypes. Here, we revisit the Ptf1aCre/+;Vglut2flox/flox mutant mouse to define fundamental phenotypes and measures that are valuable for testing the cellular, circuit, and …

Meld 3.0 Adequately Predicts Mortality And Renal Replacement Therapy Requirements In Patients With Alcohol-Associated Hepatitis, Luis Antonio Díaz, Eduardo Fuentes-López, Gustavo Ayares, Francisco Idalsoaga, Jorge Arnold, María Ayala Valverde, Diego Perez, Jaime Gómez, Rodrigo Escarate, Alejandro Villalón, Carolina A Ramírez, Maria Hernandez-Tejero, Wei Zhang, Steve Qian, Douglas A Simonetto, Joseph C Ahn, Seth Buryska, Winston Dunn, Heer Mehta, Rohit Agrawal, Joaquín Cabezas, Inés García-Carrera, Berta Cuyàs, Maria Poca, German Soriano, Shiv K Sarin, Rakhi Maiwall, Prasun K Jalal, Saba Abdulsada, Fátima Higuera-De-La-Tijera, Anand V Kulkarni, P Nagaraja Rao, Patricia Guerra Salazar, Lubomir Skladaný, Natália Bystrianska, Ana Clemente-Sanchez, Clara Villaseca-Gómez, Tehseen Haider, Kristina R Chacko, Gustavo A Romero, Florencia D Pollarsky, Juan Carlos Restrepo, Susana Castro-Sanchez, Luis G Toro, Pamela Yaquich, Manuel Mendizabal, Maria Laura Garrido, Sebastián Marciano, Melisa Dirchwolf, Victor Vargas, César Jiménez, Alexandre Louvet, Guadalupe García-Tsao, Juan Pablo Roblero, Juan G Abraldes, Vijay H Shah, Patrick S Kamath, Marco Arrese, Ashwani K Singal, Ramon Bataller, Juan Pablo Arab

Faculty, Staff and Students Publications

Background & aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH.

Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis.

Results: A total of 2,124 patients were included from 28 centres from 10 …

Exploring Gastrointestinal Health In Mecp2 Duplication Syndrome, Davut Pehlivan, Muharrem Ak, Daniel G Glaze, Bernhard Suter, Kathleen J Motil

Faculty, Staff and Students Publications

BACKGROUND: MECP2 duplication syndrome (MDS) is a rare neurogenetic syndrome caused by duplications of MECP2 at the Xq28 region. Although constipation and gastrointestinal reflux are reported in MDS, a comprehensive characterization of gastrointestinal health has not been fully explored.

METHODS: We conducted a parent survey to explore the characteristics of gastrointestinal health in individuals with MDS using a secure online registry and compared differences in gastrointestinal symptoms between individuals with MDS and those with Rett syndrome (RTT).

KEY RESULTS: One hundred six surveys were analyzed. Symptoms commonly associated with constipation occurred in 72% to 89% of MDS individuals. Eleven percent …

Avocado Consumption And Markers Of Inflammation: Results From The Multi-Ethnic Study Of Atherosclerosis (Mesa), Feon W Cheng, Nikki A Ford, Alexis C Wood, Russell Tracy

Faculty, Staff and Students Publications

Purpose

Since avocado consumption has been linked to a possible reduction in inflammation, we investigated associations between avocado consumption and markers of inflammation in a population-based multi-ethnic cohort [Multi-Ethnic Study of Atherosclerosis (MESA)].

Methods

We used a food frequency questionnaire (FFQ) at MESA exam 1 to capture avocado/guacamole consumption. To calculate daily servings of avocado/guacamole, we used both frequency and serving size data from the FFQ. We classified participants into three consumer groups: rare or never (daily serving ≤ 0.03), medium (0.03 < daily serving < 0.1), and heavy (0.1 ≤ daily serving). Inflammation was estimated by natural log-transformed inflammatory biomarkers (CRP, IL-2, IL-6, homocysteine, fibrinogen, TNF-a soluble receptors). We used multivariate general linear regression models to assess associations accounting for age, sex, race/ethnicity, educational level, income, energy intake, smoking status, physical activity, diet quality, body mass index, and diabetes type.

Results

Among 5794 MESA participants, the average age and BMI were 62.25 y ± 10.26 and 28.28 ± …

Racial Disparities In Mental Health Disorders In Youth With Chronic Medical Conditions, Vincent J Gonzalez, Rachel T Kimbro, John C Shabosky, Stefan Kostelyna, Titilope Fasipe, Natalie Villafranco, Katherine E Cutitta, Keila N Lopez

Faculty, Staff and Students Publications

OBJECTIVE: To evaluate the association between race/ethnicity, poverty, and mental health in youth with chronic conditions.

STUDY DESIGN: A cross-sectional comparative study was performed using the records of a tertiary care center from 2011 to 2015.

INCLUSION CRITERIA: children aged 4-17 years with ≥1 hospitalization or emergency department visit. Exclusion criteria were those with arrhythmias or treatment with clonidine/benzodiazepines. The primary outcome variable was diagnosis or medication for anxiety, depression, or attention deficit hyperactivity disorder. The primary predictor variable was diagnosis of cystic fibrosis (CF), sickle cell disease (SCD), or congenital heart disease (CHD).

RESULTS: We identified 112 313 patients, …

An Initial Trial Of Opt-In-Early: An Online Training Program For Caregivers Of Autistic Children, Yael G Dai, Rebecca P Thomas, Lynn Brennan, My-Linh Luu, Jamie Hughes-Lika, Molly Reilly, Paula Moreno, Brenda Obe, Kelli B Ahmed, Leandra N Berry, Robin P Goin-Kochel, Molly S Helt, Marianne L Barton, Thyde Dumont-Mathieu, Diana L Robins, Deborah A Fein

Faculty, Staff and Students Publications

Early intervention can help children learn language and improve social communication. However, many barriers, including the expense of services and an insufficient number of providers, prohibit families from accessing services when their children are young. We developed a comprehensive online program for caregivers of autistic children. The program, Online Parent Training in Early Behavioral Intervention (OPT-In-Early), uses text and video demonstrations to teach caregivers effective methods for improving their children's language, social, and adaptive skills (e.g. using utensils, toilet training), and reducing their children's disruptive behavior. Sixty-three parents from three states participated in the study. Half of the parents received …