Neuroscience and Neurobiology Commons^™

White Matter Hyperintensity Volume And Location: Associations With Wm Microstructure, Brain Iron, And Cerebral Perfusion, Christopher E. Bauer, Valentinos Zachariou, Elayna R. Seago, Brian T. Gold

Neuroscience Faculty Publications

Cerebral white matter hyperintensities (WMHs) represent macrostructural brain damage associated with various etiologies. However, the relative contributions of various etiologies to WMH volume, as assessed via different neuroimaging measures, is not well-understood. Here, we explored associations between three potential early markers of white matter hyperintensity volume. Specifically, the unique variance in total and regional WMH volumes accounted for by white matter microstructure, brain iron concentration and cerebral blood flow (CBF) was assessed. Regional volumes explored were periventricular and deep regions. Eighty healthy older adults (ages 60–86) were scanned at 3 Tesla MRI using fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), …

Healthy Dietary Intake Moderates The Effects Of Age On Brain Iron Concentration And Working Memory Performance, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Georgia Panayiotou, Edward D. Hall, D. Allan Butterfield, Brian T. Gold

Neuroscience Faculty Publications

Age-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, years of education, physical fitness and alcohol-intake. Quantitative susceptibility mapping was used for assessment of brain iron concentration and participants performed an N-Back paradigm to …

Clinical, Neuroimaging, And Molecular Spectrum Of Tecpr2-Associated Hereditary Sensory And Autonomic Neuropathy With Intellectual Disability, Sonja Neuser, Barbara Brechmann, Gali Heimer, Ines Brösse, Susanna Schubert, Lauren O'Grady, Michael Zech, Siddharth Srivastava, Shahnaz Ibrahim, Fatima Khan

Department of Paediatrics and Child Health

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus. Through international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms. A cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections, and central/nocturnal hypopnea as core manifestations. A review of brain magnetic resonance imaging scans demonstrated a …

Inflammatory Regulation Of Cns Barriers After Traumatic Brain Injury: A Tale Directed By Interleukin-1, Colleen N. Bodnar, James B. Watson, Emma K. Higgins, Ning Quan, Adam D. Bachstetter

Neuroscience Faculty Publications

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during …

Predicting Propofol-Induced Burst Suppression Using An Individualized Model-Based Approach Over Repeated Treatments, Jason C. Huang

Utah Space Grant Consortium

Our group is investigating the antidepressant effects of high-dose propofol, but dosing propofol to induce standardized changes in EEG activity (“burst suppression”) is challenging due to limited knowledge of each subject’s pharmacokinetics (PK) and pharmacodynamics (PD). In this paper, we approximated PK-PD models for propofol-induced burst suppression (PIBS), based on multiple subjects over repeated treatments. We then applied these models to predict BSR in each subject’s repeated treatment, then evaluate their predictive performances. We hypothesized that predicting BSR from a greater number of previous treatments would improve performance, but our current results are not conclusive enough to validate the hypothesis. …

Multimodal Neuroimaging Of Hiv And Aging, Brandon Lew

Theses & Dissertations

HIV infection remains a significant contributor to disease burden, and with the success of antiretroviral therapies, the population of people with HIV is aging. A growing literature suggests a relationship between HIV-infection and a profile of age advancement, most notably in molecular studies of epigenetics. However, despite the widely-known high prevalence of HIV-related brain atrophy, functional deficits, and HIV-associated neurocognitive disorder (HAND), epigenetic age advancement has not been linked to HIV-related changes in neuroimaging metrics.

We applied three neuroimaging methods, structural MRI, resting state functional MRI, and resting state MEG, to study the brain structure and function of 121 virally-suppressed …

The Influence Of Action Video Gaming Experience On The Perception Of Emotional Faces And Emotional Word Meaning, Yuening Yan, Yi Li, Xinyu Lou, Senqi Li, Yutong Yao, Diankun Gong, Weiyi Ma, Guojian Yan

General Human Environmental Sciences Faculty Publications and Presentations

Action video gaming (AVG) experience has been found related to sensorimotor and attentional development. However, the influence of AVG experience on the development of emotional perception skills is still unclear. Using behavioral and ERP measures, this study examined the relationship between AVG experience and the ability to decode emotional faces and emotional word meanings. AVG experts and amateurs completed an emotional word-face Stroop task prior to (the pregaming phase) and after (the postgaming phase) a 1 h AVG session. Within-group comparisons showed that after the 1 h AVG session, a more negative N400 was observed in both groups of participants, …

Placental Hypoxia-Inducible Factor 1 Alpha In Early-Onset Preeclampsia As A Predictor Of Future Risk In Maternal And Fetal Health, Julie Slyby, Bryce Linkous, Sarah Scott, Chandni Chandiramani, Amy Hwang, Danielle Spanbauer, Melissa R. Kaufman, Traci Rackett, Kailey Nolan, Emily Stone, Rose A. Maxwell, David N. Dhanraj, Thomas L. Brown

Medical Student Research Symposium Abstracts and Posters

Preeclampsia is a life-threatening, pregnancy-associated disorder characterized by the rapid development of hypertension with renal dysfunction. While preeclampsia generally occurs later in pregnancy, early-onset preeclampsia (EOPE) can occur much earlier and is usually more devastating. Early-onset preeclampsia is also associated with an increased risk of maternal cardiovascular and metabolic disease in mothers later in life and neurocognitive dysfunction in their offspring. EOPE is strongly associated with abnormal placental development and fetal growth restriction during pregnancy.

A Systematic Review And Meta-Analysis On The Efficacy Of Repeated Transcranial Direct Current Stimulation For Migraine, Guoshuai Cai, Zhu Xia, Leigh Charvet, Feifei Xiao, Abhishek Datta, X Michelle Androulakis

Publications and Research

Purpose: Transcranial direct current stimulation (tDCS) may have therapeutic potential in the management of migraine. However, studies to date have yielded conflicting results. We reviewed studies using repeated tDCS for longer than 4 weeks in migraine treatment, and performed meta-analysis on the efficacy of tDCS in migraine.

Methods: In this meta-analysis, we included the common outcome measurements reported across randomized controlled trials (RCTs). Subgroup analysis was performed at different post-treatment endpoints, and with different stimulation intensities and polarities.

Results: Five RCTs were included in the quantitative meta-analysis with a total of 104 migraine patients. We found a significant reduction of …

Pornography: Social, Emotional And Mental Implications Among Adolescents, William Kelly Canady

National Youth Advocacy & Resilience Conference

This presentation will explain the historical development of pornography. It will highlight four segments: 1- Porn’s impact on brain development of reward pathways, ultimately increasing the appetite for more porn. 2- Porn can be a false substitute for real intimacy, resulting in decreased sexual satisfaction with a real person and increased verbal and physical aggression. 3- Porn promotes sex trafficking, promotes multiple sex partners and reduced STD prevention. 4- A review of interventions available to assist clients in navigating a lifestyle away from pornography.

Regional N-Glycan And Lipid Analysis From Tissues Using Maldi-Mass Spectrometry Imaging, Alexandra E. Stanback, Lindsey R. Conroy, Lyndsay E. A. Young, Tara R. Hawkinson, Kia H. Markussen, Harrison A. Clarke, Derek B. Allison, Ramon C. Sun

Neuroscience Faculty Publications

N-glycans and lipids are structural metabolites that play important roles in cellular processes. Both show unique regional distribution in tissues; therefore, spatial analyses of these metabolites are crucial to our understanding of cellular physiology. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is an innovative technique that enables in situ detection of analytes with spatial distribution. This workflow details a MALDI-MSI protocol for the spatial profiling of N-glycans and lipids from tissues following application of enzyme and MALDI matrix.

For complete details on the use and execution of this protocol, please refer to Drake et al. (2018) and Andres et al. (2020).

A Pathogenic Ufsp2 Variant In An Autosomal Recessive Form Of Pediatric Neurodevelopmental Anomalies And Epilepsy, Min Ni, Bushra Afroze, Chao Xing, Chunxiao Pan, Yanqiu Shao, Ling Cai, Brandi L. Cantarel, Jimin Pei, Nick V. Grishin, Stacy Hewson

Department of Paediatrics and Child Health

Purpose: Neurodevelopmental disabilities are common and genetically heterogeneous. We identified a homozygous variant in the gene encoding UFM1-specific peptidase 2 (UFSP2), which participates in the UFMylation pathway of protein modification. UFSP2 variants are implicated in autosomal dominant skeletal dysplasias, but not neurodevelopmental disorders. Homozygosity for the variant occurred in eight children from four South Asian families with neurodevelopmental delay and epilepsy. We describe the clinical consequences of this variant and its effect on UFMylation.
Methods: Exome sequencing was used to detect potentially pathogenic variants and identify shared regions of homozygosity. Immunoblotting assessed protein expression and post-translational modifications in patient-derived fibroblasts. …

Neuroglobin And Its Role In The Recovery Of Neuronal Cells In Hypoxic Conditions Using Hypoxia Inducible Factor– 1, Riya Shah

Honors Undergraduate Theses

Stroke is the world's leading cause of adult disability, caused by lack of oxygen and nutrients to the brain due to a blood clot in a major artery. This leads to ischemic damage of neuronal cells that leads to paralysis, motor, and speech deficits. While most stroke therapies aim at removing or reducing the blood clots in the brain, few treatments target cell damage. Neuroglobin (NGB) is a protein in the brain that is able to aid in neuroprotection following oxidative stress. Hypoxia-Inducible Factor-1 (HIF-1) is a transcription factor that serves as a marker for cell recovery after hypoxia or …

Open Neuroscience Initiative, Austin Lim

College of Science and Health Full Text Publications

The Open Neuroscience Initiative is a free-to-use textbook

This project began as a means to overcoming the financial burden that face undergraduate neuroscience students when buying textbooks. By compiling and writing a completely free-to-access textbook that covers the foundations of a typical college introduction to neuroscience course, students would have one less obstacle to overcome in their educational career, allowing them to focus their valuable time and attention on learning rather than finances. To make this project a reality, I began with a humble tweet in May 2019 that managed to gain a tiny bit of traction among the neuroscience …

Opioid Use Disorder: The Timeline For Medication Assisted Therapy, Alexander Cristofori

Capstone Showcase

Opioid Use Disorder is patterns of opioid use leading to withdrawal, giving up important life events in order to use opioids, and excessive time spent using opioids, to name a few diagnostic criteria. The clinical progression of the disorder involves periods of acute exacerbation and remission that are cyclic in nature. Treatment is most effective when it includes both pharmacological and psychosocial modalities, referred to as medication assisted therapy (MAT). Three drugs used commonly in MAT-based treatment for OUD from oldest to newest include Methadone, Buprenorphine-naloxone, and Naltrexone. Treatment program models that prioritize total abstinence from the addictive substance attached …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports (ETD)

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

How Does Direct Volunteering Affect The Onset Of Alzheimer’S Dementia In Elderly Patients With Preexisting Cardiac Comorbidities?, Sneha R. Gade

Undergraduate Research Posters

Alzheimer's Dementia is a disease that affects memory, thinking, and behavior. The Alzheimer's Association reported Alzheimer's as the sixth-leading cause of death in the United States, and a cure does not exist. Donepezil, a cholinesterase inhibitor drug, is frequently prescribed to treat Alzheimer's disease. Still, patients must continuously take the medication for years to receive any measurable improvement in quality of life after developing Alzheimer's Dementia. Further, research shows prolonged use of Donepezil can lead to other health problems, such as QTc prolongation, for cardiac disease patients. Therefore, the effectiveness of non-drug interventions, such as volunteering to prevent the disease's …

Beyond Low-Earth Orbit: Characterizing Immune And Microrna Differentials Following Simulated Deep Spaceflight Conditions In Mice, Amber M. Paul, Margareth Cheng-Campbell, Elizabeth A. Blaber, Sulekha Anand, Sharmila Bhattacharya

Publications

Spaceflight missions can cause immune system dysfunction in astronauts with little understanding of immune outcomes in deep space. This study assessed immune responses in mice following ground-based, simulated deep spaceflight conditions, compared with data from astronauts on International Space Station missions. For ground studies, we simulated microgravity using the hindlimb unloaded mouse model alone or in combination with acute simulated galactic cosmic rays or solar particle events irradiation. Immune profiling results revealed unique immune diversity following each experimental condition, suggesting each stressor results in distinct circulating immune responses, with clear consequences for deep spaceflight. Circulating plasma microRNA sequence analysis revealed …

Cortical Iron Disrupts Functional Connectivity Networks Supporting Working Memory Performance In Older Adults, Valentinos Zachariou, Christopher E. Bauer, Elayna R. Seago, Flavius D. Raslau, David K. Powell, Brian T. Gold

Neuroscience Faculty Publications

Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control …

Network-Level Mechanisms Underlying Effects Of Transcranial Direct Current Stimulation (Tdcs) On Visuomotor Learning, Pejman Sehatpour, Clément Dondé, Matthew J. Hoptman, Johanna Kreither, Devin Adair, Elisa Dias, Blair Vail, Stephanie Rohrig, Gail Silipo, Javier Lopez-Calderon, Antigona Martinez, Daniel C. Javitt

Publications and Research

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation approach in which low level currents are administered over the scalp to influence underlying brain function. Prevailing theories of tDCS focus on modulation of excitation-inhibition balance at the local stimulation location. However, network level effects are reported as well, and appear to depend upon differential underlying mechanisms. Here, we evaluated potential network-level effects of tDCS during the Serial Reaction Time Task (SRTT) using convergent EEG- and fMRI-based connectivity approaches. Motor learning manifested as a significant (p <.0001) shift from slow to fast responses and corresponded to a significant increase in beta-coherence (p <.0001) and fMRI connectivity (p <.01) particularly within the visual-motor pathway. Differential patterns of tDCS effect were observed within different parametric task versions, consistent with network models. Overall, these findings demonstrate objective physiological effects of tDCS at the network level that result in effective behavioral modulation when tDCS parameters are matched to network-level requirements of the underlying task.

Applications Of Non-Invasive Neuromodulation For The Management Of Disorders Related To Covid-19, Abrahão Fontes Baptista, Adriana Baltar, Alexandre Hideki Okano, Alexandre Moreira, Ana Carolina Pinheiro Campos, Ana Mércia Fernandes, André Russowsky Brunoni, Bashar W. Badran, Clarice Tanaka, Daniel Ciampi De Andrade, Daniel Gomes Da Silva Machado, Edgard Morya, Eduardo Trujillo, Jaiti K. Swami, Joan A. Camprodon, Katia Monte-Silva, Katia Nunes Sá, Isadora Nunes, Juliana Barbosa Goulardins, Marom Bikson, Pedro Sudbrack-Oliveira, Priscila De Carvalho, Rafael Jardim Duarte-Moreira, Rosana Lima Pagano, Samuel Katsuyuki Shinjo, Yossi Zana

Publications and Research

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19.

Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders.

Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders.

Results: …

Historical Trauma Response Scores As A Function Of Unresolved Grief And Substance Use Disorder In American Indian Populations, Andrew R. Saunders

Undergraduate Research Symposium

Abstract

Researchers are interested in the outcomes of interventions, specifically, measuring historical trauma (HT) among American Indian/Alaska Native communities and the long-term distress and substance abuse as a result of historical trauma response (HTR). Previous literature has implicated limitations in the clinical conceptualization of the relationship between intergenerational transfer of HTR and substance abuse. The aim of the current study is to examine treatment efficacy of 50 homosexual, American Indian males randomized to a culturally-adapted juxtaposition of (1) Group Interpersonal Psychotherapy (IPT), (2) Cognitive Processing Therapy (CPT), and (3) Historical Trauma and Unresolved Grief Intervention (HTUG), or (4) waitlisted on …

Update On The Use Of Transcranial Electrical Brain Stimulation To Manage Acute And Chronic Covid-19 Symptoms, Giuseppina Pilloni, Marom Bikson, Bashar W. Badran, Mark S. George, Steven A. Kautz, Alexandre Hideki Okano, Abrahão Fontes Baptista, Leigh E. Charvet

Publications and Research

The coronavirus disease 19 (COVID-19) pandemic has resulted in the urgent need to develop and deploy treatment approaches that can minimize mortality and morbidity. As infection, resulting illness, and the often prolonged recovery period continue to be characterized, therapeutic roles for transcranial electrical stimulation (tES) have emerged as promising non-pharmacological interventions. tES techniques have established therapeutic potential for managing a range of conditions relevant to COVID-19 illness and recovery, and may further be relevant for the general management of increased mental health problems during this time. Furthermore, these tES techniques can be inexpensive, portable, and allow for trained self-administration. Here, …

Neutrophil-To-Lymphocyte Ratio: A Biomarker To Monitor The Immune Status Of Astronauts, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Sulekha Anand, Brian E. Crucian, Sharmila Bhattacharya

Publications

A comprehensive understanding of spaceflight factors involved in immune dysfunction and the evaluation of biomarkers to assess in-flight astronaut health are essential goals for NASA. An elevated neutrophil-to-lymphocyte ratio (NLR) is a potential biomarker candidate, as leukocyte differentials are altered during spaceflight. In the reduced gravity environment of space, rodents and astronauts displayed elevated NLR and granulocyte-to-lymphocyte ratios (GLR), respectively. To simulate microgravity using two well-established ground-based models, we cultured human whole blood-leukocytes in high-aspect rotating wall vessels (HARV-RWV) and used hindlimb unloaded (HU) mice. Both HARV-RWV simulation of leukocytes and HU-exposed mice showed elevated NLR profiles comparable to spaceflight …

Axonal Blockage With Microscopic Magnetic Stimulation, Hui Ye

Biology: Faculty Publications and Other Works

Numerous neurological dysfunctions are characterized by undesirable nerve activity. By providing reversible nerve blockage, electric stimulation with an implanted electrode holds promise in the treatment of these conditions. However, there are several limitations to its application, including poor bio-compatibility and decreased efficacy during chronic implantation. A magnetic coil of miniature size can mitigate some of these problems, by coating it with biocompatible material for chronic implantation. However, it is unknown if miniature coils could be effective in axonal blockage and, if so, what the underlying mechanisms are. Here we demonstrate that a submillimeter magnetic coil can reversibly block action potentials …

Integrating Affect Perception Tasks From The New York Emotion Battery Into A Comprehensive Measure Of Neuropsychological Change Across The Lifespan, Melinda A. Cornwell

Dissertations, Theses, and Capstone Projects

Background: The ability to perceive others’ emotions is a vital skill for social competency, impacting the success of personal and professional relationships (Brinton & Fujiki, 2011; Cassidy et al., 1992; Côté & Miners, 2006). According to Socioemotional Selectivity Theory (SST; Carstensen, 1991), human motivation develops to become more discerning in choosing milieus that yield the most gratifying return on the investment of personal resources (e.g., time, attention, and effort), perhaps explaining why some research findings indicate that older adults may demonstrate an affect perception (AP) bias described as a positivity effect (Reed et al., 2014). Moreover, AP predicts cognitive and …

Comparison Of Longitudinal Changes In Resting State Functional Magnetic Resonance Imaging Between Alzheimer’S And Healthy Controls, Berk Can Yilmaz

Theses

Resting State Functional Magnetic Resonance Imaging (rs-fMRI) is a technique that is widely used for analyzing brain function using different approaches and methods. This study involves rs-fMRI analysis of Blood Oxygenation Level Dependent (BOLD) signals acquired from Alzheimer’s disease (AD) Patients and Healthy Controls (HC). Each subject in the study had both functional and anatomical images with at least one rs-fMRI scan with their Anatomical (T1) scans. Previous rs-fMRI studies have demonstrated that AD shows differences in Amplitude of Low Frequency (<0.1 Hz) Fluctuations (ALFF), and Regional Homogeneity (ReHo) measures according to HCs.

The aim of the study is to investigate individual and group level differences using ReHo and mALFF related …

Optimization And Validation Of A Modified Radial-Arm Water Maze Protocol Using A Murine Model Of Mild Closed Head Traumatic Brain Injury, Teresa Macheda, Kelly N. Roberts, Josh M. Morganti, David J. Braun, Adam D. Bachstetter

Spinal Cord and Brain Injury Research Center Faculty Publications

Cognitive impairments can be a significant problem after a traumatic brain injury (TBI), which affects millions worldwide each year. There is a need for establish reproducible cognitive assays in rodents to better understand disease mechanisms and to develop therapeutic interventions towards treating TBI-induced impairments. Our goal was to validate and standardize the radial arm water maze (RAWM) test as an assay to screen for cognitive impairments caused by TBI. RAWM is a visuo-spatial learning test, originally designed for use with rats, and later adapted for mice. The present study investigates whether test procedures, such us the presence of extra-maze cues …

Direct Delivery Of Antisense Oligonucleotides To The Middle And Inner Ear Improves Hearing And Balance In Usher Mice, Jennifer J. Lentz, Bifeng Pan, Abhilash Ponnath, Christopher M. Tran, Carl Nist-Lund, Alice Galvin, Hannah Goldberg, Katelyn N. Robillard, Francine M. Jodelka, Hamilton E. Farris, Jun Huang, Tianwen Chen, Hong Zhu, Wu Zhou, Frank Rigo, Michelle L. Hastings, Gwenaëlle S.G. Géléoc

School of Medicine Faculty Publications

Usher syndrome is a syndromic form of hereditary hearing impairment that includes sensorineural hearing loss and delayed-onset retinitis pigmentosa (RP). Type 1 Usher syndrome (USH1) is characterized by congenital profound sensorineural hearing impairment and vestibular areflexia, with adolescent-onset RP. Systemic treatment with antisense oligonucleotides (ASOs) targeting the human USH1C c.216G>A splicing mutation in a knockin mouse model of USH1 restores hearing and balance. Herein, we explore the effect of delivering ASOs locally to the ear to treat hearing and vestibular dysfunction associated with Usher syndrome. Three localized delivery strategies were investigated in USH1C mice: inner ear injection, trans-tympanic membrane …

Dha Modulates Manf And Trem2 Abundance, Enhances Neurogenesis, Reduces Infarct Size, And Improves Neurological Function After Experimental Ischemic Stroke, Ludmila Belayev, Sung Ha Hong, Raul S. Freitas, Hemant Menghani, Shawn J. Marcell, Larissa Khoutorova, Pranab K. Mukherjee, Madigan M. Reid, Reinaldo B. Oria, Nicolas G. Bazan

School of Medicine Faculty Publications

Aims: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a secretory neurotrophic factor protein that promotes repair after neuronal injury. The microglia cell surface receptor (triggering receptor expressed on myeloid cells-2; TREM2) regulates the production of pro- and antiinflammatory mediators after stroke. Here, we study MANF and TREM2 expression after middle cerebral artery occlusion (MCAo) and explore if docosahexaenoic acid (DHA) treatment exerts a potentiating effect. Methods: We used 2 hours of the MCAo model in rats and intravenously administered DHA or vehicle at 3 hours after the onset of MCAo. Neurobehavioral assessment was performed on days 1, 3, 7, and 14; …