Neurosciences Commons^™

Promoting Diverse Perspectives: Addressing Health Disparities Related To Alzheimer's And All Dementias, Gladys Maestre, Carl Hill, Percy Griffin, Stephen Hall, William Hu, Jason Flatt, Ganesh Babulal

School of Medicine Publications

Dementia research lacks appropriate representation of diverse groups who often face substantial adversity and greater risk of dementia. Current research participants are primarily well-resourced, non-Hispanic White, cisgender adults who live close to academic medical centers where much of the research is based. Consequently, the field faces a knowledge gap about Alzheimer's-related risk factors in those other groups. The Alzheimer's Association hosted a virtual conference on June 14–16, 2021, supported in part by the National Institute on Aging (R13 AG072859-01), focused on health disparities. The conference was held entirely online and consisted of 2 days of core programming and a day …

Outcomes Of Extracorporeal Cardiopulmonary Resuscitation For In-Hospital Cardiac Arrest Among Children With Noncardiac Illness Categories, Morgann Loaec, Adam S Himebauch, Ron Reeder, Jessica S Alvey, Jonathan A Race, Lillian Su, Javier J Lasa, Julia C Slovis, Tia T Raymond, Ryan Coleman, Bradley J Barney, Todd J Kilbaugh, Alexis A Topjian, Robert M Sutton, Ryan W Morgan

Faculty, Staff and Students Publications

Objectives: The objective of this study was to determine the association of the use of extracorporeal cardiopulmonary resuscitation (ECPR) with survival to hospital discharge in pediatric patients with a noncardiac illness category. A secondary objective was to report on trends in ECPR usage in this population for 20 years.

Design: Retrospective multicenter cohort study.

Setting: Hospitals contributing data to the American Heart Association's Get With The Guidelines-Resuscitation registry between 2000 and 2021.

Patients: Children (< 18 yr) with noncardiac illness category who received greater than or equal to 30 minutes of cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest.

Interventions: None.

Measurements and main results: Propensity score weighting balanced ECPR and conventional CPR (CCPR) groups on hospital and patient characteristics. Multivariable logistic regression incorporating …

Novel Approach To Difficult Spinal Reconstruction: Bilateral Simultaneous Rib And Iliac Crest Vascularized Bone Graft Spinoplastic Surgery, Maria Shvedova, Isra Abdulwadood, Daniel M Vernik, Max A Shrout, Jonathan L Jeger, Dylon C Buchanan, Alexander Ropper, Sebastian Winocour, Michael Bohl, Maziyar A Kalani, Edward M Reece

Faculty, Staff and Students Publications

Pseudoarthrosis is a severe complication of spinal fusion surgery with occurrence rates as high as 35%-40%. Current options of revision surgery to correct pseudoarthrosis frequently carry high failure rates and risk of developing junctional kyphosis. Pedicled vascularized bone grafts (VBGs) are an innovative approach to boost spinal fusion rates via improving structural integrity and increasing the delivery of blood to the donor site. This versatile technique can be performed at different spinal levels without additional skin incisions and with minimal added operative time. Here we present the first bilateral rib and iliac crest VBG spinoplastic surgery performed to augment spinal …

Cognitive Function Remains Associated With Functional Impairment In Profound Dementia: Alzheimer Disease And Dementia With Lewy Bodies, Ihika Rampalli, Valory N Pavlik, Melissa M Yu, Jeffrey Bishop, Chi-Ying R Lin

Faculty, Staff and Students Publications

Background and objectives: The Baylor Profound Mental Status Examination (BPMSE) was developed to assess cognitive function in the profound stage of dementia. The Clinical Dementia Rating (CDR) scale has been widely used in measuring functional performance in dementia. We aimed to determine whether cognitive function is related to overall functional impairment in profound dementia.

Methods: We selected 864 patients with probable Alzheimer disease (AD) and 25 patients with possible dementia with Lewy Bodies (DLB) cases with profound dementia by Mini-Mental Status Examination or/and clinical global impression. We used BPMSE to measure cognitive function and the CDR sum-of-boxes (CDR-SB) score to …

Dissection, Histological Processing, And Gene Expression Analysis Of Murine Supraclavicular Brown Adipose Tissuejove: Peer Reviewed Scientific Video Journal Article Protocols, Mark G Waterstraat, Ziyi Wang, Mari Kogiso, Rommel Caballero-Juarez, Miao-Hsueh Chen

Faculty, Staff and Students Publications

Brown adipose tissue (BAT)-mediated thermogenesis plays an important role in the regulation of metabolism, and its morphology and function can be greatly impacted by environmental stimuli in mice and humans. Currently, murine interscapular BAT (iBAT), which is located between two scapulae in the upper dorsal flank of mice, is the main BAT depot used by research laboratories to study BAT function. Recently, a few previously unknown BAT depots were identified in mice, including one analogous to human supraclavicular brown adipose tissue. Unlike iBAT, murine supraclavicular brown adipose tissue (scBAT) is situated in the intermediate layer of the neck and thus …

A Therapeutically Targetable Positive Feedback Loop Between Nc-Hlx-2-7, Hlx, And Myc That Promotes Group 3 Medulloblastoma, Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Brigette Romero, Mona Batish, Stacie Stapleton, George Jallo, Elayaraja Kolanthai, Sudipta Seal, Olivier Saulnier, Michael D Taylor, Robert J Wechsler-Reya, Charles G Eberhart, Ranjan J Perera

Faculty, Staff and Students Publications

Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-lnc-HLX-2-7) inhibits tumor growth by 40%-50% in an intracranial MB xenograft mouse …

Dissociating Reading And Auditory Comprehension In Persons With Aphasia, Rachael M. Harrington, Sigfus Kristinsson, Janina Wilmskoetter, Natalie Busby, Dirk B. Den Ouden, Chris Rorden, Julius Fridriksson, Leonardo Bonilha

Communication Sciences and Disorders Faculty Articles and Research

Language comprehension is often affected in individuals with post-stroke aphasia. However, deficits in auditory comprehension are not fully correlated with deficits in reading comprehension and the mechanisms underlying this dissociation remain unclear. This distinction is important for understanding language mechanisms, predicting long-term impairments and future development of treatment interventions. Using comprehensive auditory and reading measures from a large cohort of individuals with aphasia, we evaluated the relationship between aphasia type and reading comprehension impairments, the relationship between auditory versus reading comprehension deficits and the crucial neuroanatomy supporting the dissociation between post-stroke reading and auditory deficits. Scores from the Western Aphasia …

Dopamine Lesions Alter The Striatal Encoding Of Single-Limb Gait, Long Yang, Deepak Singla, Alexander K Wu, Katy A Cross, Sotiris C Masmanidis

Faculty, Staff and Student Publications

The striatum serves an important role in motor control, and neurons in this area encode the body's initiation, cessation, and speed of locomotion. However, it remains unclear whether the same neurons also encode the step-by-step rhythmic motor patterns of individual limbs that characterize gait. By combining high-speed video tracking, electrophysiology, and optogenetic tagging, we found that a sizable population of both D1 and D2 receptor expressing medium spiny projection neurons (MSNs) were phase-locked to the gait cycle of individual limbs in mice. Healthy animals showed balanced limb phase-locking between D1 and D2 MSNs, while dopamine depletion led to stronger phase-locking …

Tmem106b Coding Variant Is Protective And Deletion Detrimental In A Mouse Model Of Tauopathy, George A Edwards, Caleb A Wood, Yang He, Quynh Nguyen, Peter J Kim, Ruben Gomez-Gutierrez, Kyung-Won Park, Yong Xu, Cody Zurhellen, Ismael Al-Ramahi, Joanna L Jankowsky

Duncan NRI Faculty and Staff Publications

TMEM106B is a risk modifier of multiple neurological conditions, where a single coding variant and multiple non-coding SNPs influence the balance between susceptibility and resilience. Two key questions that emerge from past work are whether the lone T185S coding variant contributes to protection, and if the presence of TMEM106B is helpful or harmful in the context of disease. Here, we address both questions while expanding the scope of TMEM106B study from TDP-43 to models of tauopathy. We generated knockout mice with constitutive deletion of TMEM106B, alongside knock-in mice encoding the T186S knock-in mutation (equivalent to the human T185S variant), and …

Ongoing Study Of The Association Of Apoe Gene Polymorphisms With Cognitive Impairment In The Rio Grande Valley Hispanic Population, Jaime Miguel L. Saveron, Daniela Gamez, Chun Xu

Research Symposium

Background: Alzheimer's disease (AD), a prevalent neurodegenerative disorder, exhibits a significant genetic component. In addition, mild cognitive impairment (MCI) is a key risk factor for AD. While certain demographic factors and genetic variants associated with AD and cognitive impairment have been identified in non-Hispanic populations, limited research exists on this subject within the Hispanic population, particularly in the Rio Grande Valley. This study aims to investigate the relationship between the APOE gene, specifically its ε4 allele, and cognitive impairment in the Hispanic population of the Rio Grande Valley.

Methods: A total of 269 Hispanic subjects, aged 60 and above, with …

Childhood Cancer Mutagenesis Caused By Transposase-Derived Pgbd5, Makiko Yamada, Ross R Keller, Rodrigo Lopez Gutierrez, Daniel Cameron, Hiromichi Suzuki, Reeti Sanghrajka, Jake Vaynshteyn, Jeffrey Gerwin, Francesco Maura, William Hooper, Minita Shah, Nicolas Robine, Phillip Demarest, N Sumru Bayin, Luz Jubierre Zapater, Casie Reed, Steven Hébert, Ignas Masilionis, Ronan Chaligne, Nicholas D Socci, Michael D Taylor, Claudia L Kleinman, Alexandra L Joyner, G Praveen Raju, Alex Kentsis

Faculty, Staff and Students Publications

Genomic rearrangements are a hallmark of most childhood tumors, including medulloblastoma, one of the most common brain tumors in children, but their causes remain largely unknown. Here, we show that PiggyBac transposable element derived 5 (Pgbd5) promotes tumor development in multiple developmentally accurate mouse models of Sonic Hedgehog (SHH) medulloblastoma. Most Pgbd5-deficient mice do not develop tumors, while maintaining normal cerebellar development. Ectopic activation of SHH signaling is sufficient to enforce cerebellar granule cell progenitor-like cell states, which exhibit Pgbd5-dependent expression of distinct DNA repair and neurodevelopmental factors. Mouse medulloblastomas expressing Pgbd5 have increased numbers of somatic structural DNA rearrangements, …

Tumor Treating Fields Suppress Tumor Cell Growth And Neurologic Decline In Models Of Spinal Metastases, Daniel Ledbetter, Romulo Augusto Andrade De Almeida, Xizi Wu, Ariel Naveh, Chirag B Patel, Queena Gonzalez, Thomas H Beckham, Robert North, Laurence Rhines, Jing Li, Amol Ghia, David Aten, Claudio Tatsui, Christopher Alvarez-Breckenridge

Faculty, Staff and Student Publications

Spinal metastases can result in severe neurologic compromise and decreased overall survival. Despite treatment advances, local disease progression is frequent, highlighting the need for novel therapies. Tumor treating fields (TTFields) impair tumor cell replication and are influenced by properties of surrounding tissue. We hypothesized that bone's dielectric properties will enhance TTFields-mediated suppression of tumor growth in spinal metastasis models. Computational modeling of TTFields intensity was performed following surgical resection of a spinal metastasis and demonstrated enhanced TTFields intensity within the resected vertebral body. Additionally, luciferase-tagged human KRIB osteosarcoma and A549 lung adenocarcinoma cell lines were cultured in demineralized bone grafts …

Mapping Sca1 Regional Vulnerabilities Reveals Neural And Skeletal Muscle Contributions To Disease, Lisa Duvick, W Michael Southern, Kellie A Benzow, Zoe N Burch, Hillary P Handler, Jason S Mitchell, Hannah Kuivinen, Udaya Gadiparthi, Praseuth Yang, Alyssa Soles, Carrie A Sheeler, Orion Rainwater, Shannah Serres, Erin B Lind, Tessa Nichols-Meade, Yun You, Brennon O'Callaghan, Huda Y Zoghbi, Marija Cvetanovic, Vanessa C Wheeler, James M Ervasti, Michael D Koob, Harry T Orr

Duncan NRI Faculty and Staff Publications

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, …

A Tough Bioadhesive Hydrogel Supports Sutureless Sealing Of The Dural Membrane In Porcine And Ex Vivo Human Tissue, Kyle C Wu, Benjamin R Freedman, Phoebe S Kwon, Matthew Torre, Daniel O Kent, Wenya Linda Bi, David J Mooney

Duncan NRI Faculty and Staff Publications

Complete sequestration of central nervous system tissue and cerebrospinal fluid by the dural membrane is fundamental to maintaining homeostasis and proper organ function, making reconstruction of this layer an essential step during neurosurgery. Primary closure of the dura by suture repair is the current standard, despite facing technical, microenvironmental, and anatomic challenges. Here, we apply a mechanically tough hydrogel paired with a bioadhesive for intraoperative sealing of the dural membrane in rodent, porcine, and human central nervous system tissue. Tensile testing demonstrated that this dural tough adhesive (DTA) exhibited greater toughness with higher maximum stress and stretch compared with commercial …

Exploring Neuroplasticity Changes In Neurotoxin-Induced Parkinson’S Disease: A Preliminary Analysis Using Transcranial Magnetic Stimulation, Tomas Gomez Jr., Daniel Salinas, Kelsey Potter-Baker, Nawaz Hack, Ramu Vadukapuram

Research Symposium

Background: Parkinson’s disease (PD) is a neurodegenerative condition that affects movement, cognition, gait, and significantly impacts one's quality of life. Studies have suggested that neurotoxin pre-exposure is related to PD pathology and progressive motor/non-motor deficits, though it remains unclear how neurotoxin exposure affects neuroplasticity. The present study aimed to examine neurotoxin–induced PD-associated neuroplasticity changes in relationship to mental acuity and PD motor functionalities.

Methods: 7 voluntary participants experiencing early-stage PD symptoms with self-reported neurotoxin pre-exposure were enrolled in the longitudinal, repeated-measures clinical study; 2 sex-matched, age-matched, and occupation-matched healthy subjects were recruited for controlled comparative analysis (n=9). UTRGV’s Institute …

Gamma-Aminobutyric Acid (Gaba) Neurons And Perineuronal Nets (Pnn) In The Monodelphis Domestica And Relevance To Psychiatric Disorders, Jatziry Z. Luna Escobedo, Mariela Garcia, John L. Vandeberg, Mario Gil

Research Symposium

Background/ Purpose: Gamma-aminobutyric acid (GABA) is an amino acid that serves as the central nervous system’s (CNS) main inhibitory neurotransmitter. By inhibiting nerve transmission, it works to lower neuronal excitability. Altered GABA levels have been associated with a variety of psychiatric disorders, for example Epilepsies, Parkinson’s Disease, and Schizophrenia. Perineuronal nets (PNN) are extracellular molecules that are released by neurons and glial cells that modulate many neuronal and glial functions by encapsulating the inhibitory cells and neurites. Altered PNN levels serve as a potential trigger to synaptic imbalance. The purpose of this study is to quantify and analyze the presence, …

Contribution Of 24-H Blood Pressure Variability To Dementia-Related Disorders In Hispanics, Nura Salhadar, Kristina Vatcheva, Silvia Mejia-Arango Dr., Luis J. Mena, Ney Alliey-Rodriguez, Carlos A. Chavez, Ciro A. Goana, Egle Silva, Gustavo Calmon, Rosa P. Mavarez, Joseph H. Lee, Joseph D. Terwilliger, Jesus D. Melgarejo, Gladys E. Maestre

Research Symposium

Introduction: As the number of people living with dementia is increasing at alarming rates worldwide, there is an urgent need to understand the physiopathology of dementia syndromes. Among the most important preventable risk factors, treatment of vascular risk factors such as high blood pressure (BP) decreases the risk of Alzheimer’s disease and related dementias (ADRD). Recent evidence suggests that examining BP variability provides additional physiopathological and predictive information above the mean BP level. However, studies examining the relationship between 24-h BP variability and ADRD are limited, and evidence of the association with dementia has not been documented yet. Therefore, we …

Brain-Specific Serine/Threonine-Protein Kinase 1 Is A Substrate Of Protein Kinase C Epsilon Involved In Sex-Specific Ethanol And Anxiety Phenotypes, Michael P. Dugan, Rajani Maiya, Caleb Fleischer, Michal Bajo, Angela E. Snyder, Ashwin Koduri, Sathvik Srinivasan, Marisa Roberto, Robert O. Messing

School of Graduate Studies Faculty Publications

Protein kinase C epsilon (PKCε) regulates behavioural responses to ethanol and plays a role in anxiety-like behaviour, but knowledge is limited on downstream substrates of PKCε that contribute to these behaviours. We recently identified brain-specific serine/threonine-protein kinase 1 (BRSK1) as a substrate of PKCε. Here, we test the hypothesis that BRSK1 mediates responses to ethanol and anxiety-like behaviours that are also PKCε dependent. We used in vitro kinase assays to further validate BRSK1 as a substrate of PKCε and used Brsk1−/− mice to assess the role of BRSK1 in ethanol- and anxiety-related behaviours and in physiological responses to ethanol. We …

Automated Seizure Detection Based On State-Space Model Identification, Zhuo Wang, Michael Sperling, Dale Wyeth, Allon Guez

Department of Neuroscience Faculty Papers

In this study, we developed a machine learning model for automated seizure detection using system identification techniques on EEG recordings. System identification builds mathematical models from a time series signal and uses a small number of parameters to represent the entirety of time domain signal epochs. Such parameters were used as features for the classifiers in our study. We analyzed 69 seizure and 55 non-seizure recordings and an additional 10 continuous recordings from Thomas Jefferson University Hospital, alongside a larger dataset from the CHB-MIT database. By dividing EEGs into epochs (1 s, 2 s, 5 s, and 10 s) and …

Case Report: Molecular Profiling Facilitates The Diagnosis Of A Challenging Case Of Lung Cancer With Choriocarcinoma Features, Hui Li, Xin Hu, Matthew S Ning, Gregory N Fuller, John M Stewart, Jared C Gilliam, Jia Wu, Xiuning Le, Ara A Vaporciyan, J Jack Lee, Don L Gibbons, John V Heymach, Andrew Futreal, Jianjun Zhang

Faculty, Staff and Student Publications

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as "metastatic choriocarcinoma" (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of …