Neurosciences Commons^™

Multiomic And Clinical Analysis Of Multiply Recurrent Meningiomas Reveals Risk Factors, Underlying Biology, And Insights Into Evolution, Sangami Pugazenthi, Bhuvic Patel, Collin W English, William A Leidig, Kyle P Mcgeehan, Colin R Mccornack, Shinghei Mok, Markus Anzaldua-Campos, Shervin Hosseingholi Nouri, Kaleigh Roberts, Ajay Chatrath, A Khan, Ron Gadot, Hiroko Yano, Tiemo J Klisch, Akdes S Harmanci, Akash J Patel, Albert H Kim

Faculty, Staff and Students Publications

An important subset of meningiomas behaves aggressively and is characterized by multiple recurrences. We identify clinical, genetic, and epigenetic predictors of multiply recurrent meningiomas (MRMs) and evaluate the evolution of these meningiomas in patient-matched samples. On multivariable binomial logistic regression, MRMs were significantly associated with male sex (P = 0.012), subtotal resection (P = 0.001), higher number of meningiomas on presentation (P = 0.017), and histopathological sheeting (P = 0.002). Multiomic analysis of primary meningiomas revealed that MRMs have greater copy number losses (P = 0.0313) and increased DNA methylation (P = 0.0155). In …

Cortical Acetylcholine Dynamics Are Predicted By Cholinergic Axon Activity And Behavior State, Erin Neyhart, Na Zhou, Brandon R Munn, Robert G Law, Cameron Smith, Zakir H Mridha, Francisco A Blanco, Guochuan Li, Yulong Li, Ming Hu, Matthew J Mcginley, James M Shine, Jacob Reimer

Faculty, Staff and Students Publications

Acetylcholine (ACh) is thought to play a role in driving the rapid, spontaneous brain-state transitions that occur during wakefulness; however, the spatiotemporal properties of cortical ACh activity during these state changes are still unclear. We perform simultaneous imaging of GRAB-ACh sensors, GCaMP-expressing basal forebrain axons, and behavior to address this question. We observed a high correlation between axon and GRAB-ACh activity around periods of locomotion and pupil dilation. GRAB-ACh fluorescence could be accurately predicted from axonal activity alone, and local ACh activity decreased at farther distances from an axon. Deconvolution of GRAB-ACh traces allowed us to account for sensor kinetics …

Integrated Electrophysiological And Genomic Profiles Of Single Cells Reveal Spiking Tumor Cells In Human Glioma, Rachel N Curry, Qianqian Ma, Malcolm F Mcdonald, Yeunjung Ko, Snigdha Srivastava, Pey-Shyuan Chin, Peihao He, Brittney Lozzi, Prazwal Athukuri, Junzhan Jing, Su Wang, Arif O Harmanci, Benjamin Arenkiel, Xiaolong Jiang, Benjamin Deneen, Ganesh Rao, Akdes Serin Harmanci

Faculty, Staff and Students Publications

Prior studies have described the complex interplay that exists between glioma cells and neurons, however, the electrophysiological properties endogenous to tumor cells remain obscure. To address this, we employed Patch-sequencing on human glioma specimens and found that one third of patched cells in IDH mutant (IDHmut) tumors demonstrate properties of both neurons and glia by firing single, short action potentials. To define these hybrid cells (HCs) and discern if they are of tumoral origin, we developed a computational tool, Single Cell Rule Association Mining (SCRAM), to annotate each cell individually. SCRAM revealed that HCs represent tumor and non-tumor cells that …

Alzheimer’S Disease Risk Gene Cd2ap Is A Dose-Sensitive Determinant Of Synaptic Structure And Plasticity, Matea Pavešković, Ruth B De-Paula, Shamsideen A Ojelade, Evelyne K Tantry, Mikhail Y Kochukov, Suyang Bao, Surabi Veeraragavan, Alexandra R Garza, Snigdha Srivastava, Si-Yuan Song, Masashi Fujita, Duc M Duong, David A Bennett, Philip L De Jager, Nicholas T Seyfried, Mary E Dickinson, Jason D Heaney, Benjamin R Arenkiel, Joshua M Shulman

Duncan NRI Faculty and Staff Publications

CD2-Associated protein (CD2AP) is a candidate susceptibility gene for Alzheimer's disease, but its role in the mammalian central nervous system remains largely unknown. We show that CD2AP protein is broadly expressed in the adult mouse brain, including within cortical and hippocampal neurons, where it is detected at pre-synaptic terminals. Deletion of Cd2ap altered dendritic branching and spine density, and impaired ubiquitin-proteasome system activity. Moreover, in mice harboring either one or two copies of a germline Cd2ap null allele, we noted increased paired-pulse facilitation at hippocampal Schaffer-collateral synapses, consistent with a haploinsufficient requirement for pre-synaptic release. Whereas conditional Cd2ap knockout in …

Identification Of An Ionic Mechanism For Erα-Mediated Rapid Excitation In Neurons, Meng Yu, Na Yin, Bing Feng, Peiyu Gao, Kaifan Yu, Hesong Liu, Hailan Liu, Yongxiang Li, Olivia Z Ginnard, Kristine M Conde, Mengjie Wang, Xing Fang, Longlong Tu, Jonathan C Bean, Qingzhuo Liu, Yue Deng, Yuxue Yang, Junying Han, Sanika V Jossy, Megan L Burt, Huey Zhong Wong, Yongjie Yang, Benjamin R Arenkiel, Yang He, Shaodong Guo, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Zhao Wang, Chunmei Wang, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

The major female ovarian hormone, 17β-estradiol (E2), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2-induced rapid excitations in multiple brain ERα …

Default Mode Network Electrophysiological Dynamics And Causal Role In Creative Thinking, Eleonora Bartoli, Ethan Devara, Huy Q Dang, Rikki Rabinovich, Raissa K Mathura, Adrish Anand, Bailey R Pascuzzi, Joshua Adkinson, Yoed N Kenett, Kelly R Bijanki, Sameer A Sheth, Ben Shofty

Faculty, Staff and Students Publications

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally directed cognition. The present study employs stereo-EEG in 13 human patients, obtaining high resolution neural recordings across multiple canonical DMN regions during two processes that have been associated with creative thinking: spontaneous and divergent thought. We probe these two DMN-associated higher cognitive functions through mind wandering and alternate uses tasks, respectively. Our results reveal DMN recruitment during both tasks, as well as a task-specific dissociation in spatiotemporal response dynamics. When compared to the fronto-parietal network, DMN activity was characterized by …

Leptomeningeal Metastases From Solid Tumors: A Society For Neuro-Oncology And American Society Of Clinical Oncology Consensus Review On Clinical Management And Future Directions, Jessica A Wilcox, Ugonma N Chukwueke, Myung-Ju Ahn, Ayal A Aizer, Tejus A Bale, Dieta Brandsma, Priscilla K Brastianos, Susan Chang, Mariza Daras, Peter Forsyth, Livia Garzia, Michael Glantz, Isabella C Glitza Oliva, Priya Kumthekar, Emilie Le Rhun, Seema Nagpal, Barbara O'Brien, Elena Pentsova, Eudocia Quant Lee, Jan Remsik, Roberta Rudà, Inna Smalley, Michael D Taylor, Michael Weller, Jeffrey Wefel, Jonathan T Yang, Robert J Young, Patrick Y Wen, Adrienne A Boire

Faculty, Staff and Students Publications

Leptomeningeal metastases (LM) are increasingly becoming recognized as a treatable, yet generally incurable, complication of advanced cancer. As modern cancer therapeutics have prolonged the lives of patients with metastatic cancer, specifically in patients with parenchymal brain metastases, treatment options, and clinical research protocols for patients with LM from solid tumors have similarly evolved to improve survival within specific populations. Recent expansions in clinical investigation, early diagnosis, and drug development have given rise to new unanswered questions. These include leptomeningeal metastasis biology and preferred animal modeling, epidemiology in the modern cancer population, ensuring validation and accessibility of newer leptomeningeal metastasis diagnostics, …

Neuron-Glial Interactions: Implications For Plasticity, Behavior, And Cognition, Mauricio Rangel-Gomez, Cristina M Alberini, Benjamin Deneen, Gabrielle T Drummond, Tiina Manninen, Mriganka Sur, Aleksandra Vicentic

Faculty, Staff and Students Publications

The traditional view of glial cells as mere supportive tissue has shifted, due to advances in technology and theoretical conceptualization, to include a diversity of other functions, such as regulation of complex behaviors. Astrocytes, the most abundant glial cells in the central nervous system (CNS), have been shown to modulate synaptic functions through gliotransmitter-mediated neurotransmitter reuptake, influencing neuronal signaling and behavioral functions. Contemporary studies further highlight astrocytes' involvement in complex cognitive functions. For instance, inhibiting astrocytes in the hippocampus can lead to memory deficits, suggesting their integral role in memory processes. Moreover, astrocytic calcium activity and astrocyte-neuron metabolic coupling have …

Simultaneous Ipsilateral Hip And Knee Dislocation: Management And Outcome – A Case Report, Christian G Falgons, Stephen J Warner

Faculty, Staff and Student Publications

Case: This clinical case report presents a 40-year-old male who sustained an ipsilateral hip and knee dislocation with ipsilateral femoral head fracture and incomplete femoral neck fracture following a motorcycle collision.

Conclusion: This report describes acute and later definitive orthopedic care and management, with focus on urgent interventions and timing of immediate treatments. Given the presented patient's favorable clinical outcomes, return to baseline activities, and absence of significant sequelae following injury, the considerations from the acute management and surgical planning of this patient's injuries can be used as a reference for treating the rare injury of ipsilateral knee and hip …

Cerebellar Deep Brain Stimulation As A Dual-Function Therapeutic For Restoring Movement And Sleep In Dystonic Mice, Luis E Salazar Leon, Linda H Kim, Roy V Sillitoe

Duncan NRI Faculty and Staff Publications

Dystonia arises with cerebellar dysfunction, which plays a key role in the emergence of multiple pathophysiological deficits that range from abnormal movements and postures to disrupted sleep. Current therapeutic interventions typically do not simultaneously address both the motor and non-motor symptoms of dystonia, underscoring the necessity for a multi-functional therapeutic strategy. Deep brain stimulation (DBS) is effectively used to reduce motor symptoms in dystonia, with existing parallel evidence arguing for its potential to correct sleep disturbances. However, the simultaneous efficacy of DBS for improving sleep and motor dysfunction, specifically by targeting the cerebellum, remains underexplored. Here, we test the effect …

Piezo Ion Channels: Force Sensors Of The Interoceptive Nervous System, Yasmeen M F Hamed, Britya Ghosh, Kara L Marshall

Duncan NRI Faculty and Staff Publications

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery …

Tau Is Required For Glial Lipid Droplet Formation And Resistance To Neuronal Oxidative Stress, Lindsey D Goodman, Isha Ralhan, Xin Li, Shenzhao Lu, Matthew J Moulton, Ye-Jin Park, Pinghan Zhao, Oguz Kanca, Ziyaneh S Ghaderpour Taleghani, Julie Jacquemyn, Joshua M Shulman, Kanae Ando, Kai Sun, Maria S Ioannou, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism. We found that overexpressing Tau in glia disrupts LDs in flies and rat neuron-astrocyte co-cultures, sensitizing the glia to toxic, neuronal LPOs. Using a new fly tau loss-of-function allele and RNA-mediated interference, we found that endogenous Tau is required for glial LD formation and protection against neuronal LPOs. Similarly, …

Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial …

Does Glial Lipid Dysregulation Alter Sleep In Alzheimer’S And Parkinson’S Disease?, Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

In this opinion article, we discuss potential connections between sleep disturbances observed in Alzheimer's disease (AD) and Parkinson's disease (PD) and the dysregulation of lipids in the brain. Research using Drosophila has highlighted the role of glial-mediated lipid metabolism in sleep and diurnal rhythms. Relevant to AD, the formation of lipid droplets in glia, which occurs in response to elevated neuronal reactive oxygen species (ROS), is required for sleep. In disease models, this process is disrupted, arguing a connection to sleep dysregulation. Relevant to PD, the degradation of neuronally synthesized glucosylceramides by glia requires glucocerebrosidase (GBA, a PD-associated risk factor) …

Author Correction: Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

No abstract provided.

Disruption Of Neural Periodicity Predicts Clinical Response After Deep Brain Stimulation For Obsessive-Compulsive Disorder, Nicole R Provenza, Sandesh Reddy, Anthony K Allam, Sameer V Rajesh, Nabeel Diab, Gabriel Reyes, Rose M Caston, Kalman A Katlowitz, Ajay D Gandhi, Raphael A Bechtold, Huy Q Dang, Ricardo A Najera, Nisha Giridharan, Katherine E Kabotyanski, Faiza Momin, Mohammed Hasen, Garrett P Banks, Brian J Mickey, Brent M Kious, Ben Shofty, Benjamin Y Hayden, Jeffrey A Herron, Eric A Storch, Ankit B Patel, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high …

Does Delaying Levodopa Prevent Motor Complications In Parkinson's Disease? A Meta-Analysis, Luis Guilherme Ramanzini, Julia M Frare, Luís F M Camargo, Juliana O F Silveira, Joseph Jankovic

Faculty, Staff and Students Publications

Background: There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson's disease (PD).

Objectives: We performed a meta-analysis on randomized clinical trials (RCTs) that compared early- versus delayed-start treatment with levodopa in PD.

Methods: A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non-randomized comparisons from follow-up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias.

Results: Seven studies with a total …

On The Power Of Constructive Criticism, Anna Devor, Androu Abdalmalak, Taner Akkin, Yeka Aponte, George J. Augustine, Sabrina Brigadoi, Erin M. Buckley, Robert E. Campbell, Stefan A. Carp, Jean-Yves Chatton, Jerry L. Chen, Ji-Xin Cheng, Tomáš Cižmár, Robert J. Cooper, Ippeita Dan, Patrick J. Drew, Turgut Durduran, Valentina Emiliani, Tommaso Fellin, Amanda J. Foust, Ling Fu, Amir Gandjbakhche, Judit Gervain, Ariel Gilad, Edgar Guevara Codina, Xue Han, Elizabeth M. Hillman, Ute Hochgeschwender, Song Hu, Na Ji, Prakash Kara, Beop-Min Kim, Tiffany S. Ko, Duygu Kuzum, Jérôme Lecoq, Rickson C. Mesquita, Timothy H. Murphy, U. Valentin Nägerl, Nozomi Nishimura, Yumie Ono, Nisan Ozana, Francesco S. Pavone, Darcy S. Peterka, Ferruccio Pisanello, Anna Wang Roe, Andy Y. Shih, Shy Shoham, François St-Pierre, Sungho Tak, Lin Tian, Kai Wang, Martin Wolf, Ji Yi, Ofer Yizhar, Meryem A. Yucel

Faculty, Staff and Students Publications

The editorial discusses the practice of peer review for SPIE Neurophotonics.

Feature Extraction For Generative Medical Imaging Evaluation: New Evidence Against An Evolving Trend, Mckell Woodland, Austin Castelo, Mais Al Taie, Jessica Albuquerque Marques Silva, Mohamed Eltaher, Frank Mohn, Alexander Shieh, Suprateek Kundu, Joshua P Yung, Ankit B Patel, Kristy K Brock

Faculty, Staff and Students Publications

Fréchet Inception Distance (FID) is a widely used metric for assessing synthetic image quality. It relies on an ImageNet-based feature extractor, making its applicability to medical imaging unclear. A recent trend is to adapt FID to medical imaging through feature extractors trained on medical images. Our study challenges this practice by demonstrating that ImageNet-based extractors are more consistent and aligned with human judgment than their RadImageNet counterparts. We evaluated sixteen StyleGAN2 networks across four medical imaging modalities and four data augmentation techniques with Fréchet distances (FDs) computed using eleven ImageNet or RadImageNet-trained feature extractors. Comparison with human judgment via visual …

Long-Term Efficacy And Safety Of Cannabidiol In Patients With Tuberous Sclerosis Complex: 3-Year Results From The Cannabidiol Expanded Access Program, Arie Weinstock, E Martina Bebin, Daniel Checketts, Gary D Clark, Jerzy P Szaflarski, Laurie E Seltzer, Elizabeth A Thiele, Farhad Sahebkar

Faculty, Staff and Students Publications

OBJECTIVE: The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC.

METHODS: Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. …

Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello

Faculty, Staff and Students Publications

BACKGROUND: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity.

METHODS AND RESULTS: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in …

Neuronal Alpha-Synuclein Disease Integrated Staging System Performance In Ppmi, Pasadena, And Spark Baseline Cohorts, Tien Dam, Gennaro Pagano, Michael C Brumm, Caroline Gochanour, Kathleen L Poston, Daniel Weintraub, Lana M Chahine, Christopher Coffey, Caroline M Tanner, Catherine M Kopil, Yuge Xiao, Sohini Chowdhury, Luis Concha-Marambio, Peter Dibiaso, Tatiana Foroud, Mark Frasier, Danna Jennings, Karl Kieburtz, Kalpana Merchant, Brit Mollenhauer, Thomas J Montine, Kelly Nudelman, John Seibyl, Todd Sherer, Andrew Singleton, Diane Stephenson, Matthew Stern, Claudio Soto, Eduardo Tolosa, Andrew Siderowf, Billy Dunn, Tanya Simuni, Kenneth Marek, Parkinson’S Progression Markers Initiative Collaborators

Faculty, Staff and Student Publications

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and applied biologic and clinical data-informed definitions for the NSD-ISS across the disease continuum. Individuals enrolled as Parkinson's disease, Prodromal, or Healthy Controls were defined and staged based on biological, clinical, and functional anchors at baseline. Across the three studies 1741 participants had SAA data and of these 1030 (59%) were S+ consistent …

Usf2 And Tfeb Compete In Regulating Lysosomal And Autophagy Genes, Jaebeom Kim, Young Suk Yu, Yehwa Choi, Do Hui Lee, Soobin Han, Junhee Kwon, Taichi Noda, Masahito Ikawa, Dongha Kim, Hyunkyung Kim, Andrea Ballabio, Keun Il Kim, Sung Hee Baek

Duncan NRI Faculty and Staff Publications

Autophagy, a highly conserved self-digestion process crucial for cellular homeostasis, is triggered by various environmental signals, including nutrient scarcity. The regulation of lysosomal and autophagy-related processes is pivotal to maintaining cellular homeostasis and basal metabolism. The consequences of disrupting or diminishing lysosomal and autophagy systems have been investigated; however, information on the implications of hyperactivating lysosomal and autophagy genes on homeostasis is limited. Here, we present a mechanism of transcriptional repression involving upstream stimulatory factor 2 (USF2), which inhibits lysosomal and autophagy genes under nutrient-rich conditions. We find that USF2, together with HDAC1, binds to the CLEAR motif within lysosomal …

Strategic Stabilization Of Arousal Boosts Sustained Attention, Jan Willem De Gee, Zakir Mridha, Marisa Hudson, Yanchen Shi, Hannah Ramsaywak, Spencer Smith, Nishad Karediya, Matthew Thompson, Kit Jaspe, Hong Jiang, Wenhao Zhang, Matthew J Mcginley

Duncan NRI Faculty and Staff Publications

Arousal and motivation interact to profoundly influence behavior. For example, experience tells us that we have some capacity to control our arousal when appropriately motivated, such as staying awake while driving a motor vehicle. However, little is known about how arousal and motivation jointly influence decision computations, including if and how animals, such as rodents, adapt their arousal state to their needs. Here, we developed and show results from an auditory, feature-based, sustained-attention task with intermittently shifting task utility. We use pupil size to estimate arousal across a wide range of states and apply tailored signal detection theoretic, hazard function …

Protocol For The Derivation Of Primary Cancer Stem Cell Lines From Human Ependymal Tumors, Cory M Richman, Peter B Dirks, Michael D Taylor, Kulandaimanuvel Antony Michealraj

Faculty, Staff and Students Publications

Cancer stem cells (CSCs) established from surgical biopsies closely mimic the human context and can be used to investigate disease mechanisms, genetic fitness, and therapeutic evaluation. Here, we present a protocol for the derivation of primary patient-derived CSC lines from ependymal tumors. We describe the necessary steps, from surgical intervention and biopsy to the dissociation of ependymomas to derive cultures. We then detail procedures for cell line propagation and define the characteristics of these primary cancer cell lines. For complete details on the use and execution of this protocol, please refer to Michealraj et al.

Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean

Journal of the South Carolina Academy of Science

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments and non-motor symptoms, significantly impacting patients' quality of life. Currently, cerebrospinal fluid (CSF) is the primary biofluid used for PD biomarker studies, notably α-synuclein, despite the invasive nature of lumbar puncture procedures. Recent work has shown that some of these PD biomarkers have been measured in saliva. As an alternative to CSF, saliva can be non-invasively self-collected by patients repeatedly over time to monitor biomarker levels. However, the stability of these biomarkers in saliva needs to be evaluated before saliva can be considered for patient self-collection studies. Therefore, …

A Novel Non-Invasive Murine Model Of Neonatal Hypoxic-Ischemic Encephalopathy Demonstrates Developmental Delay And Motor Deficits With Activation Of Inflammatory Pathways In Monocytes, Elise A Lemanski, Bailey A Collins, Andrew T Ebenezer, Sudha Anilkumar, Victoria A Langdon, Qi Zheng, Shanshan Ding, Karl Royden Franke, Jaclyn M Schwarz, Elizabeth Wright-Jin

Department of Medicine Faculty Papers

Neonatal hypoxic-ischemic encephalopathy (HIE) occurs in 1.5 per 1000 live births, leaving affected children with long-term motor and cognitive deficits. Few animal models of HIE incorporate maternal immune activation (MIA) despite the significant risk MIA poses to HIE incidence and diagnosis. Our non-invasive model of HIE pairs late gestation MIA with postnatal hypoxia. HIE pups exhibited a trend toward smaller overall brain size and delays in the ontogeny of several developmental milestones. In adulthood, HIE animals had reduced strength and gait deficits, but no difference in speed. Surprisingly, HIE animals performed better on the rotarod, an assessment of motor coordination. …

Pre-Hospital Stroke Time Intervals In The Rio Grande Valley, Kelsey Baker, Elio E. Garcia Sosa

Research Colloquium

Background and Introduction: Stroke continues to be a significant cause of mortality in the United States. Despite advancements in acute stroke treatments such as thrombolytic therapy and endovascular procedures, many patients remain unable to benefit from these interventions due to delays in receiving treatment. Healthcare professionals have made substantial efforts to improve 'door to needle' times, the interval between a patient's arrival at the hospital and the administration of thrombolytic therapy, yielding promising outcomes. However, a critical gap persists: the time interval from the onset of stroke symptoms to when patients actually present at a healthcare facility. This study aims …

1-Year Outcomes Of Resolute Onyx Zotarolimus-Eluting Stent For Symptomatic Intracranial Atherosclerotic Disease: A Multicenter Propensity Score-Matched Comparison With Stenting Versus Aggressive Medical Management For Preventing Recurrent Stroke In Intracranial Stenosis Trial, Saisree Ravi, Ibrahim A Bhatti, Ravi S Nunna, Syed Khalid, Wondwossen G Tekle, Omar Tanweer, Jan-Karl Burkhardt, Pascal M Jabbour, Stavropoula I Tjoumakaris, Nabeel A Herial, Adnan H Siddiqui, Ramesh Grandhi, Adnan I Qureshi, Farhan Siddiq, Ameer E Hassan

Faculty, Staff and Students Publications

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is one of the most prevalent causes of stroke across the world. Endovascular treatment has gained prominence but remains a challenge with unfavorable results. Recent literature has demonstrated that the Resolute Onyx Zotarolimus-Eluting Stent (RO-ZES) is a technically safe option with low complication rates along with 30-day outcomes associated with intracranial stent placement for ICAD with RO-ZES compared to results from the Stenting Versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial. Here, we aim to compare outcomes at one year with the SAMMPRIS trial with a multicenter longitudinal study.

MATERIALS …

The Effect Of Intravenous Thrombolysis In Stroke Patients With Unsuccessful Thrombectomy, Sameh Samir Elawady, Rahim Abo Kasem, Hidetoshi Matsukawa, Conor Cunningham, Mohamed Mahdi Sowlat, Noah Lee Nawabi, Atakan Orscelik, Joshua M Venegas, Julio Isidor, Hasna Loulida, Ilko Maier, Pascal Jabbour, Joon-Tae Kim, Stacey Quintero Wolfe, Ansaar Rai, Robert M Starke, Marios-Nikos Psychogios, Edgar A Samaniego, Nitin Goyal, Shinichi Yoshimura, Hugo Cuellar, Brian Howard, Ali Alawieh, Ali Alaraj, Mohamad Ezzeldin, Daniele G Romano, Omar Tanweer, Justin Mascitelli, Isabel Fragata, Adam Polifka, Fazeel Siddiqui, Joshua Osbun, Ramesh Grandhi, Roberto Crosa, Charles Matouk, Min S Park, Michael R Levitt, Waleed Brinjikji, Mark Moss, Ergun Daglioglu, Richard Williamson, Pedro Navia, Peter Kan, Reade De Leacy, Shakeel Chowdhry, David J Altschul, Alejandro M Spiotta, Sami Al Kasab

Faculty, Staff and Students Publications

BACKGROUND: The benefit of intravenous thrombolysis (IVT) is well established. We aim to study the benefits of IVT in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) who underwent unsuccessful mechanical thrombectomy (MT).

METHODS: We included AIS patients who underwent MT for anterior circulation LVO with failed recanalization (modified treatment in cerebral ischemia [mTICI] score ≤ 2A). Patients who received IVT prior to MT were compared to those who received MT alone. Propensity score matching using demographic, clinical, radiographic and procedural variables was used to match patients with and without IVT. The primary outcome was favorable 90-day good …