Neurology Commons^™

Administration Of Electroconvulsive Therapy For Depression Associated With Deep Brain Stimulation In A Patient With Post-Traumatic Parkinson's Disease: A Case Study, Miles G. Cunningham, Golnaz Yadollahikhales, Gordana Vitaliano, Craig Van Horne

Neurosurgery Faculty Publications

Background: Deep brain stimulation (DBS) has been shown to be effective for parkinsonian symptoms poorly responsive to medications. DBS is typically well-tolerated, as are the maintenance battery changes. Here we describe an adverse event during a battery replacement procedure that caused rapid onset of severe depression.

Case Presentation: The patient is a 58-year-old woman who was in a serious motor vehicle accident and sustained a concussion with loss of consciousness. Within weeks of the accident she began developing parkinsonian symptoms that progressively worsened over the subsequent 10 years. Responding poorly to medications, she received DBS, which controlled her movement symptoms. …

Spinal Cord Injury And Autonomic Dysreflexia- A Case Report, Apurva Bhatt, Brit Moore, Talal Asif, Kristy E. Steigerwalt, Rebecca R. Pauly

Marshall Journal of Medicine

Autonomic dysreflexia (AD) is a life threatening condition affecting patients with spinal cord lesions T6 level and above. A 51 year old male with a history of paraplegia due to a C6 spinal cord injury (30 years prior) presented with recurrent debilitating episodic diaphoresis, hypertension, low body temperature, and bradycardia. Previous hospitalizations presumed sepsis from UTI to be the etiology, however on further evaluation his symptoms were consistent with undiagnosed AD. This article describes a unique case presentation and reviews AD in depth, including the etiology, pathophysiology and management.

Direct Current-Induced Calcium Trafficking In Different Neuronal Preparations, Andrzej Wieraszko, Zaghloul Ahmed

Publications and Research

The influence of direct current (DC) stimulation on radioactive calcium trafficking in sciatic nerve in vivo and in vitro, spinal cord, and synaptosomes was investigated. The exposure to DC enhanced calcium redistribution in all of these preparations. The effect was dependent on the strength of the stimulation and extended beyond the phase of exposure to DC. The DC-induced increase in calcium sequestration by synaptosomes was significantly reduced by cobalt and rupture of synaptosomes by osmotic shock. Although both anodal and cathodal currents were effective, the experiments with two electrodes of different areas revealed that cathodal stimulation exerted stronger effect. The …

Interleukin-17a Promotes Cd8 T Cell Cytotoxicity To Facilitate West Nile Virus Clearance, Amber M. Paul, Dhiraj Acharya, Penghua Wang, Jianfeng Dai, David Gate

Publications

CD8 T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) in inducing cytotoxic-mediator gene expression and promoting CD8 T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a/) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8 T cells isolated from Il17a/ mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in …

Biallelic Mutations In Tbcd, Encoding The Tubulin Folding Cofactor D, Perturb Microtubule Dynamics And Cause Early-Onset Encephalopathy., Elisabetta Flex, Marcello Niceta, Serena Cecchetti, Isabelle Thiffault, Margaret G. Au, Alessandro Capuano, Emanuela Piermarini, Anna A. Ivanova, Joshua W. Francis, Giovanni Chillemi, Balasubramanian Chandramouli, Giovanna Carpentieri, Charlotte A. Haaxma, Andrea Ciolfi, Simone Pizzi, Ganka V. Douglas, Kara Levine, Antonella Sferra, Maria Lisa Dentici, Rolph R. Pfundt, Jean-Baptist Lepichon, Emily G. Farrow, Frank Baas, Fiorella Piemonte, Bruno Dallapiccola, John M. Graham, Carol J. Saunders, Enrico Bertini, Richard A. Kahn, David A. Koolen, Marco Tartaglia

Manuscripts, Articles, Book Chapters and Other Papers

Microtubules are dynamic cytoskeletal elements coordinating and supporting a variety of neuronal processes, including cell division, migration, polarity, intracellular trafficking, and signal transduction. Mutations in genes encoding tubulins and microtubule-associated proteins are known to cause neurodevelopmental and neurodegenerative disorders. Growing evidence suggests that altered microtubule dynamics may also underlie or contribute to neurodevelopmental disorders and neurodegeneration. We report that biallelic mutations in TBCD, encoding one of the five co-chaperones required for assembly and disassembly of the αβ-tubulin heterodimer, the structural unit of microtubules, cause a disease with neurodevelopmental and neurodegenerative features characterized by early-onset cortical atrophy, secondary hypomyelination, microcephaly, thin …

An Ultrasensitive Electrogenerated Chemiluminescence-Based Immunoassay For Specific Detection Of Zika Virus, Amber M. Paul, Dhiraj Acharya, Pradip Bastola, Linda Le, Estenfani Fernandez, Michael S. Diamond, Wujian Miao, Fengwei Bai

Publications

Zika virus (ZIKV) is a globally emerging mosquito-transmitted flavivirus that can cause severe fetal abnormalities, including microcephaly. As such, highly sensitive, specific, and cost-effective diagnostic methods are urgently needed. Here, we report a novel electrogenerated chemiluminescence (ECL)-based immunoassay for ultrasensitive and specific detection of ZIKV in human biological fluids. We loaded polystyrene beads (PSB) with a large number of ECL labels and conjugated them with anti-ZIKV monoclonal antibodies to generate anti-ZIKV-PSBs. These anti-ZIKV-PSBs efficiently captured ZIKV in solution forming ZIKV-anti-ZIKV-PSB complexes, which were subjected to measurement of ECL intensity after further magnetic beads separation. Our results show that the anti-ZIKV-PSBs …

A Hypothesis For Using Pathway Genetic Load Analysis For Understanding Complex Outcomes In Bilirubin Encephalopathy, Sean M. Riordan, Douglas C. Bittel, Jean-Baptist Lepichon, Silvia Gazzin, Claudio Tiribelli, Jon F. Watchko, Richard P. Wennberg, Steven Shapiro

Manuscripts, Articles, Book Chapters and Other Papers

© 2016 Riordan, Bittel, Le Pichon, Gazzin, Tiribelli, Watchko, Wennberg and Shapiro.

Genetic-based susceptibility to bilirubin neurotoxicity and chronic bilirubin encephalopathy (kernicterus) is still poorly understood. Neonatal jaundice affects 60-80% of newborns, and considerable effort goes into preventing this relatively benign condition from escalating into the development of kernicterus making the incidence of this potentially devastating condition very rare in more developed countries. The current understanding of the genetic background of kernicterus is largely comprised of mutations related to alterations of bilirubin production, elimination, or both. Less is known about mutations that may predispose or protect against CNS bilirubin neurotoxicity. …

Diabetes Is Associated With Cerebrovascular But Not Alzheimer's Disease Neuropathology, Erin L. Abner, Peter T. Nelson, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Randall L. Woltjer, Nigel J. Cairns, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Kamal Masaki, Suzanne L. Tyas, David A. Bennett, Julie A. Schneider, Zoe Arvanitakis

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: The relationship of diabetes to specific neuropathologic causes of dementia is incompletely understood.

METHODS: We used logistic regression to evaluate the association between diabetes and infarcts, Braak neurofibrillary tangle stage, and neuritic plaque score in 2365 autopsied persons. In a subset of >1300 persons with available cognitive data, we examined the association between diabetes and cognition using Poisson regression.

RESULTS: Diabetes increased odds of brain infarcts (odds ratio [OR] = 1.57, P < .0001), specifically lacunes (OR = 1.71, P < .0001), but not Alzheimer's disease neuropathology. Diabetes plus infarcts was associated with lower cognitive scores at end of life than infarcts or diabetes alone, and diabetes plus high level of Alzheimer's neuropathologic changes was associated with lower mini-mental state examination scores than the pathology alone.

DISCUSSION: This study supports the conclusions that diabetes increases the risk of cerebrovascular but not Alzheimer's disease pathology, and at least some of diabetes' relationship to …

Encoding Of Saltatory Tactile Velocity In The Adult Orofacial Somatosensory System, Rebecca Custead

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Processing dynamic tactile inputs is a key function of somatosensory systems. Spatial velocity encoding mechanisms by the nervous system are important for skilled movement production and may play a role in recovery of motor function following neurological insult. Little is known about tactile velocity encoding in trigeminal networks associated with mechanosensory inputs to the face, or the consequences of movement.

High resolution functional magnetic resonance imaging (fMRI) was used to investigate the neural substrates of velocity encoding in the human orofacial somatosensory system during unilateral saltatory pneumotactile inputs to perioral hairy skin in 20 healthy adults. A custom multichannel, scalable …

Can Gait Signatures Provide Quantitative Measures For Aiding Clinical Decision-Making? A Systematic Meta-Analysis Of Gait Variability Behavior In Patients With Parkinson’S Disease, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

A disturbed, inconsistent walking pattern is a common feature of patients with Parkinson's disease (PwPD). Such extreme variability in both temporal and spatial parameters of gait has been associated with unstable walking and an elevated prevalence of falls. However, despite their ability to discretise healthy from pathological function, normative variability values for key gait parameters are still missing. Furthermore, an understanding of each parameter's response to pathology, as well as the inter-parameter relationships, has received little attention. The aim of this systematic literature review and meta-analysis was therefore to define threshold levels for pathological gait variability as well as to …

N-Acetyl Cysteine May Support Dopamine Neurons In Parkinson's Disease: Preliminary Clinical And Cell Line Data., Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Jingli Cai, Xiatao Wei, Anthony J. Bazzan, Li Zhong, Brendan Bowen, Charles Intenzo, Lorraine Iacovitti, Andrew B. Newberg

Marcus Institute of Integrative Health Faculty Papers

BACKGOUND: The purpose of this study was to assess the biological and clinical effects of n-acetyl-cysteine (NAC) in Parkinson's disease (PD).

METHODS: The overarching goal of this pilot study was to generate additional data about potentially protective properties of NAC in PD, using an in vitro and in vivo approach. In preparation for the clinical study we performed a cell tissue culture study with human embryonic stem cell (hESC)-derived midbrain dopamine (mDA) neurons that were treated with rotenone as a model for PD. The primary outcome in the cell tissue cultures was the number of cells that survived the insult …

1st Place Research Paper: The Effectiveness Of Yoga Therapy On An Adult, Post-Stroke Population: A Systematic Review, Baylor E. Hogan

Kevin and Tam Ross Undergraduate Research Prize

Objectives: The objectives of this paper are to (1) give a brief overview of stroke pathophysiology (2) outline yoga as a therapeutic strategy (3) present the current research on yoga rehabilitation for stroke (4) discuss the efficacy of yoga for chronic stroke.

Methods: Relevant terms were searched in PubMed, Web of Science, Academic OneFile, ScienceDirect, and Google Scholar electronic databases. Studies were excluded if they contained pediatric stroke, non-stroke neurological diseases, or subjects with comorbidities. Statistically significant data was extracted for the primary measures of nine trials.

Results: Four studies measured statistically significant outcomes (p<0.05). These included improvements in balance, independence, endurance, trait anxiety, fear of falling, self-efficacy, pain, strength, range of motion (ROM), activity, participation, and quality of life (QoL). Discussion: Lack of statistical significance in post-stroke depression (PSD) measures may be due to inadequate intervention length or a psychosocial cause of depression. Improvements in balance, flexibility, and strength from yoga participation permitted progress in disability and functionality. Finally, overall health-related quality of life (HRQL) is affected by the severity of mental disorders and physical disability. Yoga can have a positive effect in both domains and therefore, may improve HRQL.

Conclusion: …

Paired Associative Transspinal And Transcortical Stimulation Produces Bidirectional Plasticity Of Human Cortical And Spinal Motor Pathways, Luke Dixon, Mohamed Ibrahim, Danielle Santora

Dissertations, Theses, and Capstone Projects

Anatomical, physiological, and functional connectivity exists between primary motor cortex (M1) and spinal cord neurons. Paired associative stimulation (PAS) produces enduring changes in M1 based on the Hebbian principle of associative plasticity. The present study aims to discover immediate neurophysiological changes on human corticomotor pathways by pairing noninvasive transspinal and transcortical stimulation via transcranial magnetic stimulation (TMS). We delivered paired transspinal and transcortical stimulation for 40-min at precise interstimulus intervals with TMS being delivered after (transspinal-transcortical PAS) or before (transcortical-transspinal PAS) transspinal stimulation. Transspinal-transcortical PAS markedly decreased intracortical inhibition, increased intracortical facilitation and M1 excitability with concomitant decreases of motor …

Carotid Ultrasound Is Not Helpful In Simple Syncope, Nicholus Yee M.D., Shilin Patel M.D., Raymond Gong

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Scott JW, Schwartz AL, Gates JD, Gerhard-Herman M, Havens JM. Choosing wisely for syncope: low-value carotid ultrasound use. J Am Heart Assoc. 2014 Aug 13;3(4). pii: e001063. doi: 10.1161/JAHA.114.001063

Changes In The Adult Glun2b Associated Proteome Following Adolescent Intermittent Ethanol Exposure, H. Scott Swartzwelder, Mary-Louise Risher, Kelsey M. Miller, Roger J. Colban, Danner G. Winder, Tiffany A. Wills

Biomedical Sciences

Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive …

Revealing The Quality Of Movement: A Meta-Analysis Review To Quantify The Thresholds To Pathological Variability During Standing And Walking, Niklas König Ignasiak

Physical Therapy Faculty Articles and Research

Neuromotor processes are inherently noisy, which results in variability during movement and fluctu-ations in motor control. Although controversial, low levels of variability are traditionally considered healthy, while increased levels are thought to be pathological. This systematic review and meta-analysisof the literature investigates the thresholds between healthy and pathological task variability.

After examining 13,195 publications, 109 studies were included. Results from over 3000 healthy sub-jects and 2775 patients revealed an overall positive effect size of pathology on variability of 0.59 forwalking and 0.80 for sway. For the coefficient of variation of stride time (ST) and sway area (SA), upperthresholds of 2.6% …

Comparing Direct Factor Xa Inhibitors And Warfarin In The Prevention Of Stroke In Patients With Atrial Fibrillation, Alessandra Lof, Stephanie Pillai

Physician Assistant Capstones, 2016 to 2019

Objective: To evaluate the overall efficacy, advantages, and disadvantages of treatment with direct factor Xa inhibitors as compared to warfarin in the prevention of stroke in patients with atrial fibrillation. Methods: A quantitative meta-analysis was performed on three separate studies, each of which evaluated the efficacy and safety outcomes of a direct factor Xa inhibitor versus warfarin in preventing stroke in patients with atrial fibrillation. The direct factor Xa inhibitors that were evaluated included apixaban, edoxaban, and rivaroxaban. Results: The direct factor Xa inhibitors were found to be as effective, and in some cases more effective, than …

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

Network-Driven Plasma Proteomics Expose Molecular Changes In The Alzheimer's Brain, Philipp A. Jaeger, Kurt M. Lucin, Markus Britschgi, Badri Vardarajan, Ruo-Pan Huang, Elizabeth D. Kirby, Rachelle Abbey, Bradley F. Boeve, Adam L. Boxer, Lindsay A. Farrer, Nicole Finch, Neill R. Graff-Radford, Elizabeth Head, Matan Hofree, Ruochun Huang, Hudson Johns, Anna Karydas, David S. Knopman, Andrey Loboda, Eliezer Masliah, Ramya Narasimhan, Ronald C. Petersen, Alexei Podtelezhnikov, Suraj Pradhan, Rosa Rademakers, Chung-Huan Sun, Steven G. Younkin, Bruce L. Miller, Trey Ideker, Tony Wyss-Coray

Pharmacology and Nutritional Sciences Faculty Publications

Background: Biological pathways that significantly contribute to sporadic Alzheimer’s disease are largely unknown and cannot be observed directly. Cognitive symptoms appear only decades after the molecular disease onset, further complicating analyses. As a consequence, molecular research is often restricted to late-stage post-mortem studies of brain tissue. However, the disease process is expected to trigger numerous cellular signaling pathways and modulate the local and systemic environment, and resulting changes in secreted signaling molecules carry information about otherwise inaccessible pathological processes.

Results: To access this information we probed relative levels of close to 600 secreted signaling proteins from patients’ blood samples using …

1st Place Contest Entry: The Effectiveness Of Yoga Therapy On An Adult, Post-Stroke Population: A Systematic Review, Baylor E. Hogan

Kevin and Tam Ross Undergraduate Research Prize

This is Baylor Hogan's submission for the 2016 Kevin and Tam Ross Undergraduate Research Prize, which won first place. She wrote about the effects of yoga therapy on the physical and mental wellbeing of stroke patients. You can read the final essay that came out of her research here.

Baylor is a senior at Chapman University, majoring in Kinesiology. Her faculty mentor is Dr. Elizabeth DeBaets.

Gene Expression Profiling In An Alzheimer's Disease Mouse Model, Matthew R. Dalton

Senior Honors Theses

Explaining precisely how Alzheimer’s disease (AD)—the world’s most common form of dementia—materializes in the human brain has proven to be one of the most elusive ends in modern medicine. Progressive memory loss, neurodegeneration, and the presence of abnormal protein aggregates of amyloid-beta (Aβ) and neurofibrillary tangles (NFT) characterize this disease. Genome sequencing provides researchers with the ability to better identify disease-related changes in gene expression, some of which may play a role in the initiation and progression toward the AD-like state. Intimate interactions between tissues have been observed in many diseases, particularly between the brain and blood. This analysis seeks …

Exploring Oculomotor Trends In Collegiate Athletes, Brett Whorley, Julie A. Honaker

UCARE: Research Products

Collaborative efforts to improve athlete safety without significantly hindering the rules of the games aim to develop a novel system to better measure and diagnose concussions. Provided that common signs of concussions include blurred vision, distant gaze, and dizziness, the Dizziness and Balance Disorders Lab at UNL believes that the simple oculomotor exam studied in this project may be applied to this procedure. Within the broader goal to better understand the causes, signs, symptoms, and prognosis of concussions, researchers desired to further investigate the results of this oculomotor test. The aim was to identify and interpret correlations between collegiate athlete …

Oscillatory Neural Responses Evoked By Natural Vestibular Stimuli In Humans, Steven Gale, Mario Prsa, Aaron Schurger, Annietta Gay, Aurore Paillard, Bruno Herbelin, Jean-Philippe Guyot, Christophe Lopez, Olaf Blanke

Psychology Faculty Articles and Research

While there have been numerous studies of the vestibular system in mammals, less is known about the brain mechanisms of vestibular processing in humans. In particular, of the studies that have been carried out in humans over the last 30 years, none has investigated how vestibular stimulation (VS) affects cortical oscillations. Here we recorded high-density electroencephalography (EEG) in healthy human subjects and a group of bilateral vestibular loss patients (BVPs) undergoing transient and constant-velocity passive whole body yaw rotations, focusing our analyses on the modulation of cortical oscillations in response to natural VS. The present approach overcame significant technical challenges …

Volume Averaging Of Spectral-Domain Optical Coherence Tomography Impacts Retinal Segmentation In Children, Carmelina Trimboli-Heidler, Kelly Vogt, Robert A. Avery

GW Research Days 2016 - 2020

Purpose: To determine the influence of volume averaging on retinal layer thickness measures acquired with spectral-domain optical coherence tomography (SD-OCT) in children.

Methods: Macular SD-OCT images were acquired using three different volume acquisition settings (i.e., ART 1, 3, and 9 volumes) in children enrolled in a prospective OCT study. Total retinal, retinal nerve fiber layer, ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer plexiform layer thicknesses were measured around an ETDRS grid using beta version automated segmentation software for the Spectralis. The magnitude of manual segmentation required to correct the automated segmentation was classified as …

Micro-Rna And Mrna Profiles Associated With Ectopic Germinal Center Formation In Thymus Samples Of Patients With Autoimmune Myas, Manjistha Sengupta, Bi-Dar Wang, Norman H. Lee, Gary Cutter, Linda Louise Kusner, Henry J. Kaminski

GW Research Days 2016 - 2020

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction (NMJ). A characteristic pathology of patients with early onset MG is thymic hyperplasia with ectopic germinal centers (GC). However, mechanisms that trigger and maintain thymic hyperplasia are poorly characterized. Micro-RNAs (miRNA) are small, non-coding RNAs that are increasingly appreciated to be involved in the pathology of several autoimmune diseases. In order to determine the central mechanisms involved in the pathology, thymus samples from MG patients were assessed by histology and grouped based on appearance of GC compared to …

Role Of Slit2 In Reducing Complications After Surgical Brain Injury, Prativa Sherchan

Loma Linda University Electronic Theses, Dissertations & Projects

Surgical brain injury (SBI) is the inadvertent injury to brain tissue at the perisurgical site which occurs due to neurosurgical maneuvers such as incision, retraction, and electrocoagulation that can result in post-operative complications. Blood brain barrier (BBB) disruption and neuroinflammation are major pathophysiological consequences after neurosurgical injury. Blood brain barrier dysfunction leads to increased influx of water and plasma proteins as well as peripheral immune cell infiltration into the brain parenchyma that further potentiates brain edema and worsens post-operative neurological function. Activated resident immune cells and infiltrated peripheral immune cells release inflammatory mediators and promote oxidative stress and cell death …

Alzheimer's Biomarkers Are Correlated With Brain Connectivity In Older Adults Differentially During Resting And Task States, Yang Jiang, Haiqing Huang, Erin Abner, Lucas S. Broster, Gregory A. Jicha, Frederick A. Schmitt, Richard Kryscio, Anders H. Andersen, David Powell, Linda J. Van Eldik, Brian T. Gold, Peter T. Nelson, Charles D. Smith, Mingzhou Ding

Behavioral Science Faculty Publications

β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ₄₂ and pTau₁₈₁), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ …

Non-Alcoholic Fatty Liver Disease Induces Signs Of Alzheimer’S Disease (Ad) In Wild-Type Mice And Accelerates Pathological Signs Of Ad In An Ad Model, Do-Geun Kim, Antje Krenz, Leon E. Toussaint, Kirk J. Maurer

Dartmouth Scholarship

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease afflicting about one third of the world's population and 30 % of the US population. It is induced by consumption of high-lipid diets and is characterized by liver inflammation and subsequent liver pathology. Obesity and consumption of a high-fat diet are known to increase the risk of Alzheimer's disease (AD). Here, we investigated NAFLD-induced liver inflammation in the pathogenesis of AD.

Methods: WT and APP-Tg mice were fed with a standard diet (SD) or a high-fat diet (HFD) for 2, 5 months, or 1 year to induce NAFLD. Another …

Cannabinoid Receptor Interacting Protein Suppresses Agonist-Driven Cb1 Receptor Internalization And Regulates Receptor Replenishment In An Agonist-Biased Manner, Lawrence C. Blumes, Sandra Leone-Kabler, Deborah J. Luessen, Glenn S. Marrs, Erica Lyons, Caroline E. Bass, Rong Chen, Dana E. Selley, Allyn C. Howlett

Neurology Publications

Cannabinoid receptor interacting protein 1a (CRIP1a) is a CB1 receptor (CB1R) distal C-terminus-associated protein that modulates CB1R signaling via G proteins, and CB1R down-regulation but not desensitization (Blume et al. [2015] Cell Signal., 27, 716-726; Smith et al. [2015] Mol. Pharmacol., 87, 747-765). In this study, we determined the involvement of CRIP1a in CB1R plasma membrane trafficking. To follow the effects of agonists and antagonists on cell surface CB(1)Rs, we utilized the genetically homogeneous cloned neuronal cell line N18TG2, which endogenously expresses both CB1R and CRIP1a, and exhibits a well-characterized endocannabinoid signaling system. We developed stable CRIP1a-over-expressing and CRIP1a-siRNA-silenced knockdown …

Pharmacological Blockade Of The Calcium Plateau Provides Neuroprotection Following Organophosphate Paraoxon Induced Status Epilepticus In Rats, Laxmikant S. Deshpande, Robert E. Blair, Beverly A. Huang, Kristin F. Phillips, Robert J. Delorenzo

Neurology Publications

Organophosphate (OP) compounds which include nerve agents and pesticides are considered chemical threat agents. Currently approved antidotes are crucial in limiting OP mediated acute mortality. However, survivors of lethal OP exposure exhibit delayed neuronal injury and chronic behavioral morbidities. In this study, we investigated neuroprotective capabilities of dantrolene and carisbamate in a rat survival model of paraoxon (POX) induced status epilepticus (SE). Significant elevations in hippocampal calcium levels were observed 48-h post POX SE survival, and treatment with dantrolene (10 mg/kg, i.m.) and carisbamate (90 mg/kg, i.m.) lowered these protracted calcium elevations. POX SE induced delayed neuronal injury …