Neurology Commons^™

Therapeutic Effect Of Rho Kinase Inhibitor Fsd-C10 In A Mouse Model Of Alzheimer's Disease., Qing-Fang Gu, Jie-Zhong Yu, Hao Wu, Yan-Hua Li, Chun-Yun Liu, Ling Feng, Guang-Xian Zhang, Bao-Guo Xiao, Cun-Gen Ma

Department of Neurology Faculty Papers

Fasudil, a Rho kinase (ROCK) inhibitor, effectively inhibits disease severity in a mouse model of Alzheimer's disease (AD). However, given its significant limitations, including a relatively narrow safety window and poor oral bioavailability, Fasudil is not suitable for long-term use. Thus, screening for ROCK inhibitor(s) that are more efficient, safer, can be used orally and suitable for long-term use in the treatment of neurodegenerative disorders is required. The main purpose of the present study is to explore whether FSD-C10, a novel ROCK inhibitor, has therapeutic potential in amyloid precursor protein/presenilin-1 transgenic (APP/PS1 Tg) mice, and to determine possible mechanisms of …

Genetics Of The Thrombomodulin-Endothelial Cell Protein C Receptor System And The Risk Of Early-Onset Ischemic Stroke, John W. Cole, Huichun Xu, Kathleen Ryan,, Thomas Jaworek, Nicole Dueke, Patrick Mcardle, Brady Gaynor,, Yu-Ching Cheng, Jeffrey O'Connell, Ayeesha Kamran Kamal

Section of Neurology

Background and Purpose: Polymorphisms in coagulation genes have been associated with early-onset ischemic stroke. Here we pursue an a priori hypothesis that genetic variation in the endothelial-based receptors of the thrombomodulin-protein C system (THBD and PROCR) may similarly be associated with early-onset ischemic stroke. We explored this hypothesis utilizing a multi-stage design of discovery and replication.

Methods: Discovery was performed in the Genetics-of-Early-Onset Stroke (GEOS) Study, a biracial population-based case-control study of ischemic stroke among men and women aged 15-49 including 829 cases of first ischemic stroke (42.2% African-American) and 850 age-comparable stroke-free controls (38.1% African-American). Twenty-four single-nucleotide-polymorphisms …

Pediatric Cardioembolic Stroke In Midaortic Syndrome, Ana C. Albuja, Mauricio F. Villamar, Alejandra M. Stewart, Donita D. Lightner

Neurology Faculty Publications

No abstract provided.

Tumour Treating Fields (Ttfs) For Paediatric Brain Tumours, Brain Metastases And Other Novel Applications, Farhan Arshad Mirza, Muhammad Shahzad Shamim

Section of Neurosurgery

Tumour treating fields (TTFs) are now FDA approved for high grade glioma treatment. Novel application of this treatment modality is being assessed for paediatric brain tumours and intracranial metastatic disease. Clinical trials are being conducted to test the efficacy of this treatment modality as adjuvant therapy to current standard of care. Here we will discuss the existing literature on TTF its role in pathologies other than GBM. In addition, aspects of safety, compliance and cost are also discussed.

Leveling The Playing Field: Supporting Neurodiversity Via Virtual Realities, Louanne E. Boyd, Kendra Day, Natalia Stewart, Kaitlyn Abdo, Kathleen Lamkin, Erik J. Linstead

Mathematics, Physics, and Computer Science Faculty Articles and Research

Neurodiversity is a term that encapsulates the diverse expression of human neurology. By thinking in broad terms about neurological development, we can become focused on delivering a diverse set of design features to meet the needs of the human condition. In this work, we move toward developing virtual environments that support variations in sensory processing. If we understand that people have differences in sensory perception that result in their own unique sensory traits, many of which are clustered by diagnostic labels such as Autism Spectrum Disorder (ASD), Sensory Processing Disorder, Attention-Deficit/Hyperactivity Disorder, Rett syndrome, dyslexia, and so on, then we …

Differences Between Stance And Foot Preference Evident In Osprey (Pandion Haliaetus) Fish Holding During Movement., Laura L Allen, Katie L Morrison, Wesley A E Scott, Steve Shinn, Alan M Haltiner, Michael J Doherty

Articles, Abstracts, and Reports

BACKGROUND: Skateboarders, snowboarders, and surfers all show stance preferences for which foot is forward while moving. We are unaware of other animals than humans with a stance preference, perhaps excepting Osprey, who fly their caught fish beneath them in a foot-forward stance. We hypothesize there should be no difference between left foot forward, right foot back (conventional) versus right foot forward left foot back (goofy) stances or for fish holding with unilateral left or right foot. Online, publicly available, convenience images of Osprey catching fish were accessed and assessed by five independent reviewers using different Internet search engines or online …

Basic Considerations For The Use Of Monoclonal Antibodies In Migraine., Morris Levin, Stephen D Silberstein, Robert Gilbert, Sylvia Lucas, Leanne Munsie, Alyssa Garrelts, Kate Kennedy, Nicole Everman, Eric Pearlman

Articles, Abstracts, and Reports

BACKGROUND: Migraine impacts more than 36 million people in the United States and 1 billion people worldwide. Despite the increasing availability of acute and preventive therapies, there is still tremendous unmet need. Potential treatments in development include monoclonal antibodies (mAbs). Appropriate use of these “biologic” treatments will necessitate an understanding of the aspects that distinguish them from traditional medications.

AIM: Many drug classes are prescribed for migraine treatment, but all have limitations. Recently, calcitonin gene-related peptide (CGRP) activity has shown a significant promise as a target for preventive therapy. In this review, we provide an overview of the potential role …

Longitudinal Screening Detects Cognitive Stability And Behavioral Deterioration In Als Patients, Susan Woolley, Ray Goetz, Pam Factor-Litvak, Jennifer Murphy, Jonathan Hupf, Catherine Lomen-Hoerth, Howard Andrews, Daragh Heitzman, Richard Bedlack, Jonathan Katz, Richard Barohn, Eric Sorenson, Bjorn Oskarsson, Americo Fernandes Filho, Edward J. Kasarskis, Tahseen Mozaffar, Sharon Nations, Andrea Swenson, Agnes Koczon-Jaremko, Georgia Christodoulou, Hiroshi Mitsumoto

Neurology Faculty Publications

Objective. To evaluate longitudinal cognitive/behavioral change over 12 months in participants enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS). Methods. We analyzed data from 294 ALS participants, 134 of whom were studied serially. Change over time was evaluated controlling for age, sex, symptom duration, education, race, and ethnicity. Using multiple regression, we evaluated associations among decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and cognitive/behavioral changes. Change in cognitive/behavioral subgroups was assessed using one-way analyses of covariance. Results. Participants with follow-up data had fewer baseline behavior problems compared to patients …

Hyperhomocysteinemia As A Risk Factor For Vascular Contributions To Cognitive Impairment And Dementia, Brittani R. Price, Donna M. Wilcock, Erica M. Weekman

Physiology Faculty Publications

Behind only Alzheimer’s disease, vascular contributions to cognitive impairment and dementia (VCID) is the second most common cause of dementia, affecting roughly 10–40% of dementia patients. While there is no cure for VCID, several risk factors for VCID, such as diabetes, hypertension, and stroke, have been identified. Elevated plasma levels of homocysteine, termed hyperhomocysteinemia (HHcy), are a major, yet underrecognized, risk factor for VCID. B vitamin deficiency, which is the most common cause of HHcy, is common in the elderly. With B vitamin supplementation being a relatively safe and inexpensive therapeutic, the treatment of HHcy-induced VCID would seem straightforward; however, …

Potential Role Of Csf Cytokine Profiles In Discriminating Infectious From Non-Infectious Cns Disorders., Danielle Fortuna, D. Craig Hooper, Amity L. Roberts, Larry A. Harshyne, Michelle Nagurney, Mark T. Curtis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Current laboratory testing of cerebrospinal fluid (CSF) does not consistently discriminate between different central nervous system (CNS) disease states. Rapidly distinguishing CNS infections from other brain and spinal cord disorders that share a similar clinical presentation is critical. New approaches focusing on aspects of disease biology, such as immune response profiles that can have stimulus-specific attributes, may be helpful. We undertook this preliminary proof-of-concept study using multiplex ELISA to measure CSF cytokine levels in various CNS disorders (infections, autoimmune/demyelinating diseases, lymphomas, and gliomas) to determine the potential utility of cytokine patterns in differentiating CNS infections from other CNS diseases. Both …

Neutrophil To Lymphocyte Ratio: A Prognostic Indicator For Astronaut Health, Amber M. Paul, Siddhita D. Mhatre, Egle Cekanaviciute, Ann-Sofie Schreurs, Candice G.T. Tahimic, Ruth K. Globus, Brian Crucian, Sharmila Bhattacharya

Publications

Short-term and long-term spaceflight missions can cause immune system dysfunction in astronauts. Recent studies indicate elevated white blood cells (WBC) and polymorphonuclear neutrophils (PMN) in astronaut blood, along with unchanged or reduced lymphocyte counts, and reduced T cell function, during short-(days) and long-(months) term spaceflight. A high PMN to lymphocyte ratio (NLR) can acts as a strong predictor of poor prognosis in cancer, and as a biomarker for subclinical inflammation in humans and chronic stress in mouse models, however, the NLR has not yet been identified as a predictor of astronaut health during spaceflight. For this, complete blood cell count …

Forecast Or Fall: Prediction's Importance To Postural Control, Chris J. Dakin, David A.E. Bolton

Kinesiology and Health Science Faculty Publications

To interact successfully with an uncertain environment, organisms must be able to respond to both unanticipated and anticipated events. For unanticipated events, organisms have evolved stereotyped motor behaviors mapped to the statistical regularities of the environment, which can be trigged by specific sensory stimuli. These 'reflexive' responses are more or less hardwired to prevent falls and represent, maybe, the best available solution to maintaining posture given limited available time and information. With the gift of foresight, however, motor behaviors can be tuned or prepared in advance, improving the ability of the organism to compensate for, and interact with, the changing …

Mediterranean Diet Adherence And Rate Of Cerebral Aβ-Amyloid Accumulation: Data From The Australian Imaging, Biomarkers And Lifestyle Study Of Ageing, Stephanie Rainey-Smith, Yian Gu, Samantha Gardener, James D Doecke, Victor L Villemagne, Belinda M Brown, Kevin Taddei, Simon M Laws, Hamid R. Sohrabi, Michael Weinborn, David Ames, Christopher Fowler, S Lance Macaulay, Paul Maruff, Colin L Masters, Olivier Salvado, Christopher C Rowe, Nikolaos Scarmeas, Ralph N. Martins

Research outputs 2014 to 2021

Accumulating research has linked Mediterranean diet (MeDi) adherence with slower cognitive decline and reduced Alzheimer's disease (AD) risk. However, no study to-date has examined the relationship between MeDi adherence and accumulation of cerebral Aβ-amyloid (Aβ; a pathological hallmark of AD) in older adults. Cognitively normal healthy control participants of the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing completed the Cancer Council of Victoria Food Frequency Questionnaire at baseline, which was used to construct a MeDi score for each participant (score range 0-9; higher score indicating higher adherence). Cerebral Aβ load was quantified by Pittsburgh Compound B positron emission …

Conference Proceedings: Aurora Scientific Day 2018

Journal of Patient-Centered Research and Reviews

This journal supplement includes selected abstracts from among the more than 50 presented at the 44th annual Aurora Scientific Day research symposium. Held May 25, 2018, in Milwaukee, Wisconsin, Aurora Scientific Day provides a forum for original research conducted by faculty, fellows, residents, and other allied health professionals affiliated with Aurora Health Care, an integrated health system with hospitals and clinics in Wisconsin and Illinois.

Stress-Induced Heat Shock Protein 40 And Immune Function In Altered Gravity, Amber M. Paul, Brooke D. Shepard, Sharmila Bhattacharya

Publications

In space, astronauts are more susceptible to pathogens, viral reactivation and immunosuppression, which poses limits to their health and the mission. Interestingly, during space flight, stress-inducible heat shock proteins (HSP) are robustly induced, and the overexpression of HSPs have been implicated in immune dysregulation, therefore HSPs may be critically involved in regulating immune homeostasis. HSP40/DNAJ1 plays a major role in proper protein translation and folding. Its loss of function has been implicated in susceptibility to microbial infection, while its overexpression has been implicated in autoimmunity, collectively suggesting its complicated, but necessary, role in maintaining immunological function. To determine the role …

Manipulation Of Human Verticality Using High-Definition Transcranial Direct Current Stimulation, Taiza E. G. Santos, Diandra B. Favoretto, Iman Ghodratti Toostani, Diego C. Nascimento, Brunna P. Rimoli, Eduardo Bergonzoni, Tenysson Will Lemos, Dennis Quangvinh Truong, Alexandre C. B. Delbem, Bahador Makkiabadi, Renato Moraes, Francisco Louzada, Marom Bikson, Joao P. Leite, Dylan J. Edwards

Publications and Research

Background: Using conventional tDCS over the temporo-parietal junction (TPJ) we previously reported that it is possible to manipulate subjective visual vertical (SVV) and postural control. We also demonstrated that high-definition tDCS (HD-tDCS) can achieve substantially greater cortical stimulation focality than conventional tDCS. However, it is critical to establish dose-response effects using well-defined protocols with relevance to clinically meaningful applications.

Objective: To conduct three pilot studies investigating polarity and intensity-dependent effects of HD-tDCS over the right TPJ on behavioral and physiological outcome measures in healthy subjects. We additionally aimed to establish the feasibility, safety, and tolerability of this stimulation protocol.

Methods: …

Dual Inhibition Of Bcl-2/Bcl-Xl And Xpo1 Is Synthetically Lethal In Glioblastoma Model Systems, Enyuan Shang, Yiru Zhang, Chang Shu, Chiaki Tsuge Ishida, Elena Bianchetti, Mike-Andrew Westhoff, Georg Karpel-Massler, Markus D. Siegelin

Publications and Research

XPO1 has recently emerged as a viable treatment target for solid malignancies, including glioblastoma (GBM), the most common primary malignant brain tumor in adults. However, given that tumors become commonly resistant to single treatments, the identification of combination therapies is critical. Therefore, we tested the hypothesis that inhibition of anti-apoptotic Bcl-2 family members and XPO1 are synthetically lethal. To this purpose, two clinically validated drug compounds, the BH3-mimetic, ABT263, and the XPO1 inhibitor, Selinexor, were used in preclinical GBM model systems. Our results show that inhibition of XPO1 reduces cellular viability in glioblastoma cell cultures. Moreover, addition of ABT263 significantly …

Leukemia Inhibitory Factor Modulates The Peripheral Immune Response In A Rat Model Of Emergent Large Vessel Occlusion, Stephanie M. Davis, Lisa A. Collier, Edric D. Winford, Christopher C. Leonardo, Craig T. Ajmo Jr., Elspeth A. Foran, Timothy J. Kopper, John C. Gensel, Keith R. Pennypacker

Neurology Faculty Publications

Background: The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation of antioxidant enzymes, promotes an anti-inflammatory phenotype in several types of immune cells. The goal of this study was to determine whether LIF treatment modulates the peripheral immune response after stroke.

Methods: Young male (3 month) Sprague-Dawley rats underwent sham surgery or permanent middle cerebral artery occlusion (MCAO). Animals were administered LIF (125 μg/kg) or …

Implementation Of Aset Skin Safety Guideline By Lehigh Valley Health Network Committee Improves Extended Eeg Related Skin Breakdown, Jo Ann Coryell R. Eeg T, Cnim, Alexis Gerber R. Eeg T. Cltm, Sameh Morkous Md, Faan

Sameh Morkous, MD, FAAP, FAAN

No abstract provided.

Cd133 Expression In Glioblastoma Multiforme: A Literature Review, Syed Ijlal Ahmed, Gohar Javed, Altaf Ali Laghari, Syeda Beenish Bareeqa, Saba Farrukh, Shajeeah Zahid, Syeda Sana Samar, Kashif Aziz

Section of Neurosurgery

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most common primary brain tumor. Extensive research has been carried out to discover the factors associated with the course and progression of GBM. CD133 is a glycoprotein antigen found in normal and malignant tissues. CD133 has been recognized as a marker for the growth of cancer cells. The association between this tissue marker and GBM is being investigated. The aim of this review was to evaluate the role of CD133 as a tumor marker for the prognosis of GBM.