Neurosciences Commons^™

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Aneurysmal Subarachnoid Hemorrhage And Acute Subdural Hematoma, Neurosurgical And Endovascular Rescue. Case Report., José Omar Santellan Resident, José Ramón Aguilar Dr., Abraham Ibarra Dr., Ulises García Dr.

Archives of Neurosurgery

Introduction: Acute subdural hemorrhage (aSDH) in association with aneurismal subarachnoid hemorrhage (SAH) is a severe disease with an incidence of 0.5% to 7.9% of all SAH. Due to the rarity of aneurysmal aSDH, it remains difficult to define a comprehensive management protocol. In this case review, following the CARE guidelines, we show the hybrid management of this pathology to know the importance of using different types of neurosurgical treatments in case of two severe diseases in critical patients.

We present two patients who developed sudden onset cephalea and neurological impairment secondary to aneurysmal subarachnoid hemorrhage associated with acute subdural hematoma. …

Consciousness Explained Or Described?, Aaron Schurger, Michael S. A. Graziano

Psychology Faculty Articles and Research

Consciousness is an unusual phenomenon to study scientifically. It is defined as a subjective, first-person phenomenon, and science is an objective, third-person endeavor. This misalignment between the means—science—and the end—explaining consciousness—gave rise to what has become a productive workaround: the search for ‘neural correlates of consciousness’ (NCCs). Science can sidestep trying to explain consciousness and instead focus on characterizing the kind(s) of neural activity that are reliably correlated with consciousness. However, while we have learned a lot about consciousness in the bargain, the NCC approach was not originally intended as the foundation for a true explanation of consciousness. Indeed, it …

Short Chain Fatty Acids Taken At Time Of Thrombectomy In Acute Ischemic Stroke Patients Are Independent Of Stroke Severity But Associated With Inflammatory Markers And Worse Symptoms At Discharge, Nicholas Henry, Jacqueline A. Frank, Christopher J. Mclouth, Amanda L. Trout, Andrew J. Morris, Jianzhong Chen, Ann M. Stowe, Justin F. Fraser, Keith R. Pennypacker

Behavioral Science Faculty Publications

Introduction: Short chain fatty acids (SCFA) are gut microbiota-derived metabolites that contribute to the gut-brain axis and may impact stroke outcomes following gut dysbiosis. We evaluated plasma SCFA concentrations against stroke severity parameters and identified SCFA-associated protein networks.

Methods: The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC), a continuously enrolling tissue bank, was used to obtain stroke samples. Arterial blood distal and proximal to the thrombus was obtained from Acute Ischemic Stroke (AIS) Patients (n=53) during thrombectomy. Patient demographics, stroke presentation and outcome parameters were reported. The SCFAs were isolated from proximal plasma via chemical derivatization UHPLC coupled tandem …

Transcranial Direct Current Stimulation On Parkinson’S Disease: Systematic Review And Meta-Analysis, Paloma Cristina Alves De Oliveira, Thiago Anderson Brito De Araújo, Daniel Gomes Da Silva Machado, Abner Cardoso Rodrigues, Marom Bikson, Suellen Marinho Andrade, Alexandre Hideki Okano, Hougelle Simplicio, Rodrigo Pegado, Edgard Morya

Publications and Research

Background: Clinical impact of transcranial direct current stimulation (tDCS) alone for Parkinson’s disease (PD) is still a challenge. Thus, there is a need to synthesize available results, analyze methodologically and statistically, and provide evidence to guide tDCS in PD.

Objective: Investigate isolated tDCS effect in different brain areas and number of stimulated targets on PD motor symptoms.

Methods: A systematic review was carried out up to February 2021, in databases: Cochrane Library, EMBASE, PubMed/MEDLINE, Scopus, and Web of science. Full text articles evaluating effect of active tDCS (anodic or cathodic) vs. sham or control on motor symptoms of PD were …

Toward A Multimodal Computer-Aided Diagnostic Tool For Alzheimer’S Disease Conversion, Danilo Pena, Jessika Suescun, Mya Schiess, Timothy M. Ellmore, Luca Giancardo, Alzheimer’S Disease Neuroimaging Initiative

Publications and Research

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. It is one of the leading sources of morbidity and mortality in the aging population AD cardinal symptoms include memory and executive function impairment that profoundly alters a patient’s ability to perform activities of daily living. People with mild cognitive impairment (MCI) exhibit many of the early clinical symptoms of patients with AD and have a high chance of converting to AD in their lifetime. Diagnostic criteria rely on clinical assessment and brain magnetic resonance imaging (MRI). Many groups are working to help automate this process to improve the clinical workflow. Current …

Delayed Testosterone Treatment In A Rodent Model Of Repeat Mild Traumatic Brain Injury Attenuates Mechanisms Of Cellular Death In The Vestibular Nucleus, Michael Volyanyuk

Master's Theses

A common complaint after repetitive mild traumatic brain injury (rmTBI) is vestibular dysfunction, which can become persistent and decrease quality of life. Delayed testosterone treatment has been shown to reduce vestibular impairment and improve neuronal survival in the vestibular nucleus following rmTBI; however, the long-term molecular pathways associated with rmTBI and testosterone treatment remain widely unexplored. We utilized a 5-hit closed-head rodent rmTBI model and administered testosterone 35 days after injury (DPI). The vestibular nuclei were removed and prepared for RT-qPCR and western blotting. Gene expression and protein levels were elevated for markers of oxidative stress (NADPH oxidase 4) and …

Current And Novel Neuroregenerative Therapies, Arrin Brooks

Theses, Dissertations and Capstones

Underlying the physical and cognitive deficits consequent of many neuropathologies is one common factor, the loss of neurons. While neurodegenerative diseases, stroke, and traumatic brain injury arise from a variety of etiologies, they all ultimately result in injury and/or death of neuronal cells and concomitant functional deficits. In the present work we primarily focus on current and potential treatments for localized lesions, particularly those in the striatum of Parkinson’s disease (PD) or the cortex as in stroke. First, we discuss a new surgical technique for deep brain stimulator (DBS) placement, as DBS is a mainstay treatment for movement disorders including …

Crispr-Krispr: A Method To Identify On-Target And Random Insertion Of Donor Dnas And Their Characterization In Knock-In Mice, Masayuki Tanaka, Keiko Yokoyama, Hideki Hayashi, Sanae Isaki, Kanae Kitatani, Ting Wang, Hisako Kawata, Hideyuki Matsuzawa, Channabasavaiah B. Gurumurthy, Hiromi Miura, Masato Ohtsuka

Journal Articles: Pharmacology & Experimental Neuroscience

CRISPR tools can generate knockout and knock-in animal models easily, but the models can contain off-target genomic lesions or random insertions of donor DNAs. Simpler methods to identify off-target lesions and random insertions, using tail or earpiece DNA, are unavailable. We develop CRISPR-KRISPR (CRISPR-Knock-ins and Random Inserts Searching PRotocol), a method to identify both off-target lesions and random insertions. CRISPR-KRISPR uses as little as 3.4 μg of genomic DNA; thus, it can be easily incorporated as an additional step to genotype founder animals for further breeding.

Ecdysoneless Overexpression Drives Mammary Tumorigenesis Through Upregulation Of C-Myc And Glucose Metabolism, Bhopal C. Mohapatra, Sameer Mirza, Aditya Bele, Channabasavaiah B. Gurumurthy, Mohsin Raza, Irfana Saleem, Matthew D. Storck, Aniruddha Sarkar, Sai Sundeep Kollala, Surendra K. Shukla, Siddesh Southekal, Kay-Uwe Wagner, Fang Qiu, Subodh M. Lele, Mansour A. Alsaleem, Emad A. Rakha, Chittibabu Guda, Pankaj K. Singh, Robert D. Cardiff, Hamid Band, Vimla Band

Journal Articles: Pharmacology & Experimental Neuroscience

Ecdysoneless (ECD) protein is essential for embryogenesis, cell-cycle progression, and cellular stress mitigation with an emerging role in mRNA biogenesis. We have previously shown that ECD protein as well as its mRNA are overexpressed in breast cancer and ECD overexpression predicts shorter survival in patients with breast cancer. However, the genetic evidence for an oncogenic role of ECD has not been established. Here, we generated transgenic mice with mammary epithelium-targeted overexpression of an inducible human ECD transgene (ECDTg). Significantly, ECDTg mice develop mammary hyperplasia, preneoplastic lesions, and heterogeneous tumors with occasional lung metastasis. ECDTg tumors exhibit epithelial to mesenchymal transition …

A Neural Signature Of Regularity In Sound Is Reduced In Older Adults, Björn Herrmann, Burkhard Maess, Ingrid S. Johnsrude

Brain and Mind Institute Researchers' Publications

Sensitivity to repetitions in sound amplitude and frequency is crucial for sound perception. As with other aspects of sound processing, sensitivity to such patterns may change with age, and may help explain some age-related changes in hearing such as segregating speech from background sound. We recorded magnetoencephalography to characterize differences in the processing of sound patterns between younger and older adults. We presented tone sequences that either contained a pattern (made of a repeated set of tones) or did not contain a pattern. We show that auditory cortex in older, compared to younger, adults is hyperresponsive to sound onsets, but …

Completing The Puzzle: Why Studies In Non-Human Primates Are Needed To Better Understand The Effects Of Non-Invasive Brain Stimulation, Sebastian J. Lehmann, Brian D. Corneil

Brain and Mind Institute Researchers' Publications

Brain stimulation is a core method in neuroscience. Numerous non-invasive brain stimulation (NIBS) techniques are currently in use in basic and clinical research, and recent advances promise the ability to non-invasively access deep brain structures. While encouraging, there is a surprising gap in our understanding of precisely how NIBS perturbs neural activity throughout an interconnected network, and how such perturbed neural activity ultimately links to behaviour. In this review, we will consider why non-human primate (NHP) models of NIBS are ideally situated to address this gap in knowledge, and why the oculomotor network that moves our line of sight offers …

Effects Of The Selective Gsk3b Inhibitor, Tideglusib, On Ethanol Consumption, Anxiety-Like Behavior, Taste Preference, And Downstream Proteins, Sam Gottlieb, Douglas Bledsoe, Jessica L. Maltman, Alanna Morgan, Jennifer T. Wolstenholme, Michael F. Miles

Graduate Research Posters

Background: We have shown modulations in glycogen synthase kinase 3 beta (GSK3B) abundance or activity regulate ethanol consumption, suggesting potential as a therapeutic target for alcohol use disorder (AUD). Here we report the GSK3B inhibitor tideglusib’s actions on ethanol consumption, basal behaviors, and modulation of GSK3B targets.

Methods: C57BL/6J males and females received i.g. 200mg/kg tideglusib, except drinking-in-the-dark (males;100mg/kg i.p.). Drinking-in-the-dark (DID): Mice given 20% ethanol 4-hours, 4-days/week x 3 weeks and then i.p. tideglusib or vehicle x 4 days in a Latin Square design with ethanol consumption measured daily. Light/Dark Box: Mice gavaged with tideglusib or vehicle …

Investigating The Effects Of In-Vivo Therapeutics Hypoxia Treatment Paradigms In Neurite Outgrowth Patterns, Jae Hyun Yoo

Theses and Dissertations--Medical Sciences

Spinal cord injury, specifically in the cervical C3-C4 region of the cervical spine, contributes to impaired breathing and a diminished quality of life. Therefore it is important to find effective and safe therapeutics to restore breathing function. Indeed, there are a myriad of research being performed in addition to valuable collaboration amongst different institutions. As such, inspired by a previous experiment, we decided to test our hypothesis that an enriching environment consisting of different hypoxic environments - sustained and intermittent hypoxia alongside normoxia - would result in neurite outgrowth. Moreover, we hypothesized that sustained hypoxia would result in the greatest …

Physiological Effects Of Activity-Based Anorexia In Female Rats And An Overview Of Eating Disorders, Madelyn Uyemura

Regis University Student Publications (comprehensive collection)

The aim of this thesis is to bring AN to the foreground of conversation both in a scientific and sociological framework. Nearly 40 million Americans suffer from anxiety disorders, which is characterized by the feeling of a loss of control. In some cases, another disorder called anorexia nervosa (AN) can codevelop. AN is characterized by a refusal, and inability, to maintain a healthy body weight. Some suffering from anxiety may restrict caloric intake and increase exercise to cope with stress. This results in extreme caloric deprivation. AN can be modeled in rats using an activity-based anorexia (ABA) method. In …

Efficacy Of Prebiotic Dietary Intervention To Mitigate Risks For Dementia Via The Gut-Brain Axis, Lucille M. Yanckello

Theses and Dissertations--Pharmacology and Nutritional Sciences

Alzheimer’s disease (AD) is the most common form of dementia with various risk factors including age, environmental factors such as brain injury and genetic factors, such as the E4 allele of the Apolipoprotein gene. Presence of the APOE4 allele increases AD risk by two- to four- fold. Recent studies have shown that mild traumatic brain injury (mTBI), even without loss of consciousness, increases risk of dementia diagnosis by more than two-fold in military personnel and is also a significant environmental risk factor for developing dementia in the general population. The gut-brain axis (GBA) or bi-directional communication between the brain and …

Walking Improvement In Chronic Incomplete Spinal Cord Injury With Exoskeleton Robotic Training (Wise): A Randomized Controlled Trial, Dylan J. Edwards, Gail Forrest, Mar Cortes, Margaret M. Weightman, Cristina Sadowsky, Shuo-Hsiu Chang, Kimberly Furman, Amy Bialek, Sara Prokup, John Carlow, Leslie Vanhiel, Laura Kemp, Darrell Musick, Marc Campo, Arun Jayaraman

Research outputs 2022 to 2026

Study design:

Clinical trial.

Objective:

To demonstrate that a 12-week exoskeleton-based robotic gait training regimen can lead to a clinically meaningful improvement in independent gait speed, in community-dwelling participants with chronic incomplete spinal cord injury (iSCI).

Setting:

Outpatient rehabilitation or research institute.

Methods:

Multi-site (United States), randomized, controlled trial, comparing exoskeleton gait training (12 weeks, 36 sessions) with standard gait training or no gait training (2:2:1 randomization) in chronic iSCI ( > 1 year post injury, AIS-C, and D), with residual stepping ability. The primary outcome measure was change in robot-independent gait speed (10-meter walk test, 10MWT) post 12-week intervention. Secondary …

A Family With Neuropathies And An Mfn2 Variant, Leah Miller

Larner College of Medicine Fourth Year Advanced Integration Teaching/Scholarly Projects

BACKGROUND: The axonal subtype of Charcot-Marie-Tooth (CMT2A) is commonly caused by dominant mutations in MFN2, which encodes a protein involved in mitochondrial dynamics and axonal transport. Over 100 variants in MFN2 are reportedly pathogenic. MFN2 dysfunction yields heterogenous neuropathies which can include optic atrophy, dysautonomia and diaphragmatic/airway dysfunction.

CASE REPORT: A 52-year-old man presented with a 10-year history of burning forefoot dysthesias and orthostasis. His examination revealed reduced sensation to light touch and pinprick distally with preserved strength and reflexes. NCS/EMG demonstrated mild, symmetric axonal polyneuropathy. Autonomic testing revealed orthostatic tachycardia and postganglionic sudomotor dysfunction. Laboratory evaluation for common causes …

Emotional Component Of Pain Perception In The Medicinal Leech?, Brian D. Burrell

Animal Sentience

Crump et al. have provided a series of criteria to assess animal sentience that is focused on the perception of pain, which is known to have both sensory and emotional components. They also provide a qualitative scoring system to assess data that address the eight criteria and apply this paradigm to decapod crustaceans. The criteria laid out have the potential to be applied to other invertebrates typically thought to have sensory response to tissue damage, but no emotional component to pain perception.

An Aphasia Research Agenda – A Consensus Statement From The Collaboration Of Aphasia Trialists, Myzoon Ali, Efstathia Soroli, Luis M. T. Jesus, Madeline Cruice, Jytte Isaksen, Evy Visch-Brink, Kleanthes K. Grohmann, C. Jagoe, Tarja Kukkonen, Spyridoula Varlokosta, Carlos Hernandez-Sacristan, Vicente Rosell-Clari, Rebecca Palmer, Silvia Martinez-Ferreiro, Erin Godecke, Sarah J. Wallace, Ruth Mcmenamin, David Copland, Caterina Breitenstein, Audrey Bowen, Ann-Charlotte Laska, Katerina Hilari, Marian C. Brady

Research outputs 2014 to 2021

Coordination of international aphasia research would minimise duplication of effort, support synergistic international activities across languages and multidisciplinary perspectives, and promote high-quality conduct and reporting of aphasia research, thereby increasing the relevance, transparency, and implementation of findings. The Collaboration of Aphasia Trialists (CATs) sought to develop an aphasia research agenda to direct future research activities, based on priorities shared by people with aphasia, family members, and healthcare professionals. Our established international research network spanning 33 countries contributed to this activity. Research literature reporting the priorities of stakeholders was reviewed and synthesized (phase 1). Representatives from Working Groups on Aphasia Assessment …