Medical Specialties Commons^™

Astragaloside Iv Protects Neurons From Microglia-Mediated Cell Damage Through Promoting Microglia Polarization., Jingwen Yu, Minfang Guo, Yanhua Li, Huiyu Zhang, Zhi Chai, Qing Wang, Yuqing Yan, Jiezhong Yu, Chunyun Liu, Guang-Xian Zhang, Ma Cungen

Department of Neurology Faculty Papers

Astragaloside IV (AST-IV) is a major active ingredient of astragalus, with a neuroprotective effect. The current study is aimed to investigate the impact of AST-IV on the M1/M2 microglial activation in response to lipopolysaccharide (LPS) stimulation, how AST-IV attenuated microglia-mediated neuronal damage, and the molecular mechanisms underlying AST-IV's protection of neurons against microglia-mediated neuronal damage. Our results showed that AST-IV partially protected microglia from death evoked by LPS and downregulated the release of pro-inflammatory (M1) mediators including interleukin (IL)-1β, IL-6, tumour necrosis factor α (TNF-α) and nitric oxide, as well as the expression of Toll-like receptors 4 (TLR4), MyD88, and …

Stat3 Genotypic Variant Rs744166 And Increased Tyrosine Phosphorylation Of Stat3 In Il-23 Responsive Innate Lymphoid Cells During Pathogenesis Of Crohn's Disease, Ying Tang, Sanda A. Tan, Atif Iqbal, Jian Li, Sarah C. Glover

Department of Neurology Faculty Papers

Crohn's disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-γ-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in …

Immunomodulatory And Neuroprotective Mechanisms Of Huangqi Glycoprotein Treatment In Experimental Autoimmune Encephalomyelitis., Yanxia Xing, Binyu Liu, Yijin Zhao, Lihong Zhang, Rodolfo Thome, Huiqing Xue, Peijun Zhang, Cungen Ma

Department of Neurology Faculty Papers

Previous studies have shown that Huangqi glycoprotein (HQGP) has an anti-inflammatory effect in vitro, and suppressed experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis; however, the mechanism underlying its effect is largely unknown. In this manuscript we investigated the mechanisms by which HQGP protect mice from EAE. HQGP was extracted from Astragalus membranaceus and purified by anion-exchange and gel filtration chromatography. HQGP delayed disease onset, reduced disease severity and alleviated inflammation and demyelination in the central nervous system (CNS). Moreover, HQGP reduced the infiltration of pathogenic immune cells and increased the expression of microtubule-associated protein 2 (MAP-2) and …

Generation Of Oligodendrocyte Progenitor Cells From Mouse Bone Marrow Cells., Yuan Zhang, Xin-Yu Lu, Giacomo Casella, Jing Tian, Ze-Qing Ye, Ting Yang, Juan-Juan Han, Ling-Yu Jia, A. M. Rostami, Xing Li

Department of Neurology Faculty Papers

Oligodendrocyte progenitor cells (OPCs) are a subtype of glial cells responsible for myelin regeneration. Oligodendrocytes (OLGs) originate from OPCs and are the myelinating cells in the central nervous system (CNS). OLGs play an important role in the context of lesions in which myelin loss occurs. Even though many protocols for isolating OPCs have been published, their cellular yield remains a limit for clinical application. The protocol proposed here is novel and has practical value; in fact, OPCs can be generated from a source of autologous cells without gene manipulation. Our method represents a rapid, and high-efficiency differentiation protocol for generating …

Peripheral Synucleinopathy In A Dj1 Patient With Parkinson Disease, Cataracts, And Hearing Loss, Derek P. Narendra, Risa Isonaka, Diana Nguyen, Alice B. Schindler, Angela D. Kokkinis, Debra Ehrlich, Tanya M. Bardakjian, David S. Goldstein, Tsao-Wei Liang, Pedro Gonzalez-Alegre

Department of Neurology Faculty Papers

No abstract provided.

Brainstem Atrophy In Focal Epilepsy Destabilizes Brainstem-Brain Interactions: Preliminary Findings., Susanne G. Mueller, Lisa M. Bateman, Maromi Nei, Alica M. Goldman, Kenneth D. Laxer

Department of Neurology Faculty Papers

BACKGROUND: MR Imaging has shown atrophy in brainstem regions that were linked to autonomic dysfunction in epilepsy patients. The brainstem projects to and modulates the activation state of several wide-spread cortical/subcortical regions. The goal was to investigate 1. Impact of brainstem atrophy on gray matter connectivity of cortical/subcortical structures and autonomic control. 2. Impact on the modulation of cortical/subcortical functional connectivity.

METHODS: 11 controls and 18 patients with non-lesional focal epilepsy (FE) underwent heart rate variability (HRV) measurements and a 3 T MRI (T1 in all subjects, task-free fMRI in 7 controls/ 12 FE). The brainstem was extracted, and atrophy …

The Endocannabinoid System In Migraine: From Bench To Pharmacy And Back., Cristina Tassorelli, Rosaria Greco, Stephen D. Silberstein

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: Migraine is a common, highly disabling disorder. Its treatment involves acute and preventive therapy. Many of available preventive medications are not well tolerated, which results in poor compliance and limited effectiveness. Cannabinoids have been proposed for the treatment of migraine but their efficacy and tolerability are controversial.

RECENT FINDINGS: Cannabinoids modulate functions and activity of signaling pathways that have a key role in pain control. Growing preclinical evidence and initial clinical findings suggest that modulation of the endocannabinoid system, via endogenous or exogenous cannabinoids may be relevant for migraine via multiple mechanisms.

SUMMARY: The endocannabinoid system qualifies …

Erenumab In Chronic Migraine: Patient-Reported Outcomes In A Randomized Double-Blind Study., Richard B. Lipton, Stewart J. Tepper, Uwe Reuter, Stephen Silberstein, Walter F. Stewart, Jon Nilsen, Dean K. Leonardi, Pooja Desai, Sunfa Cheng, Daniel D. Mikol, Robert Lenz

Department of Neurology Faculty Papers

OBJECTIVE: To determine the effect of erenumab, a human monoclonal antibody targeting the calcitonin gene-related peptide receptor, on health-related quality of life (HRQoL), headache impact, and disability in patients with chronic migraine (CM).

METHODS: In this double-blind, placebo-controlled study, 667 adults with CM were randomized (3:2:2) to placebo or erenumab (70 or 140 mg monthly). Exploratory endpoints included migraine-specific HRQoL (Migraine-Specific Quality-of-Life Questionnaire [MSQ]), headache impact (Headache Impact Test-6 [HIT-6]), migraine-related disability (Migraine Disability Assessment [MIDAS] test), and pain interference (Patient-Reported Outcomes Measurement Information System [PROMIS] Pain Interference Scale short form 6b).

RESULTS: Improvements were observed for all endpoints in …

Lewy Body Dementia Association's Research Centers Of Excellence Program: Inaugural Meeting Proceedings., Bethany Peterson, Melissa Armstrong, Douglas Galasko, James E. Galvin, Jennifer Goldman, David Irwin, Henry Paulson, Daniel Kaufer, James Leverenz, Angela Lunde, Ian G. Mckeith, Andrew Siderowf, Angela Taylor, Katherine Amodeo, Matt Barrett, Kimiko Domoto-Reilly, John Duda, Stephen Gomperts, Neill Graff-Radford, Samantha Holden, Lawrence Honig, Daniel Huddleston, Carol Lippa, Irene Litvan, Carol Manning, Karen Marder, Charbel Moussa, Chiadi Onyike, Fernando Pagan, Alexander Pantelyat, Victoria Pelak, Kathleen Poston, Joseph Quinn, Irene Richard, Liana S. Rosenthal, Marwan Sabbagh, Douglas Scharre, Sharon Sha, Holly Shill, Yasar Torres-Yaghi, Tina Christie, Todd Graham, Ian Richards, Mike Koehler, Brad Boeve

Department of Neurology Faculty Papers

The first Lewy Body Dementia Association (LBDA) Research Centers of Excellence (RCOE) Investigator's meeting was held on December 14, 2017, in New Orleans. The program was established to increase patient access to clinical experts on Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), and to create a clinical trials-ready network. Four working groups (WG) were created to pursue the LBDA RCOE aims: (1) increase access to high-quality clinical care, (2) increase access to support for people living with LBD and their caregivers, (3) increase knowledge of LBD among medical and allied (or …

Human Verbal Memory Encoding Is Hierarchically Distributed In A Continuous Processing Stream., Michal T. Kucewicz, Krishnakant Saboo, Brent M. Berry, Vaclav Kremen, Laura R. Miller, Fatemeh Khadjevand, Cory S. Inman, Paul Wanda, Michael R. Sperling, Richard Gorniak, Kathryn A. Davis, Barbara C. Jobst, Bradley Lega, Sameer A. Sheth, Daniel S. Rizzuto, Ravishankar K. Iyer, Michael J. Kahana, Gregory A. Worrell

Department of Neurology Faculty Papers

Processing of memory is supported by coordinated activity in a network of sensory, association, and motor brain regions. It remains a major challenge to determine where memory is encoded for later retrieval. Here, we used direct intracranial brain recordings from epilepsy patients performing free recall tasks to determine the temporal pattern and anatomical distribution of verbal memory encoding across the entire human cortex. High γ frequency activity (65-115 Hz) showed consistent power responses during encoding of subsequently recalled and forgotten words on a subset of electrodes localized in 16 distinct cortical areas activated in the tasks. More of the high …

Study Of The Cytological Features Of Bone Marrow Mesenchymal Stem Cells From Patients With Neuromyelitis Optica., Chunsheng Yang, Yang Yang, Li Ma, Guang-Xian Zhang, Fu-Dong Shi, Yaping Yan, Guoqiang Chang

Department of Neurology Faculty Papers

Neuromyelitis optica (NMO) is a refractory autoimmune inflammatory disease of the central nervous system without an effective cure. Autologous bone marrow‑derived mesenchymal stem cells (BM‑MSCs) are considered to be promising therapeutic agents for this disease due to their potential regenerative, immune regulatory and neurotrophic effects. However, little is known about the cytological features of BM‑MSCs from patients with NMO, which may influence any therapeutic effects. The present study aimed to compare the proliferation, differentiation and senescence of BM‑MSCs from patients with NMO with that of age‑ and sex‑matched healthy subjects. It was revealed that there were no significant differences in …

Guidelines Of The International Headache Society For Controlled Trials Of Acute Treatment Of Migraine Attacks In Adults: Fourth Edition., Hans-Christoph Diener, Cristina Tassorelli, David W. Dodick, Stephen Silberstein, Richard B. Lipton, Messoud Ashina, Werner J. Becker, Michel D. Ferrari, Peter J. Goadsby, Patricia Pozo-Rosich, Shuu-Jiun Wang, Jay Mandrekar

Department of Neurology Faculty Papers

The quality of clinical trials is an essential part of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of the Guidelines for controlled trials of drugs in migraine. Scientific and clinical developments in headache medicine led to second and third editions in 2000 and 2012, respectively. The current, fourth edition of the Guidelines retains the structure and much content from previous editions. However, it also incorporates evidence from clinical trials published after the third edition as well as feedback from meetings with regulators, …

Development And Validation Of The Fsiq-Rms: A New Patient-Reported Questionnaire To Assess Symptoms And Impacts Of Fatigue In Relapsing Multiple Sclerosis, Stacie Hudgens, René Schüler, Jonathan Stokes, Sonya Eremenco, Elke Hunsche, Thomas P. Leist

Department of Neurology Faculty Papers

Objectives: A new patient-reported outcome (PRO) instrument to measure fatigue symptoms and impacts in relapsing multiple sclerosis (RMS) was developed in a qualitative stage, followed by psychometric validation and migration from paper to an electronic format.

Methods: Adult patients with relapsing-remitting multiple sclerosis (RRMS) were interviewed to elicit fatigue-related symptoms and impacts. A draft questionnaire was debriefed in cognitive interviews with further RRMS patients, and revised. Content confirmation interviews were conducted with patients with progressive-relapsing multiple sclerosis (PRMS) and relapsing secondary-progressive multiple sclerosis (RSPMS). Psychometric analyses used data from adult patients with different RMS subtypes and matched non-RMS controls in …

A Closer Look At Arsa Activity In A Patient With Metachromatic Leukodystrophy., Kathleen Doherty, S. Barron Frazier, Matthew Clark, Anna Childers, Sumit Pruthi, David A. Wenger, Jessica Duis

Department of Neurology Faculty Papers

Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease mainly caused by a deficiency of arylsulfatase A activity. The typical clinical course of patients with the late infantile form includes a regression in motor skills with progression to dysphagia, seizures, hypotonia and death. We present a case of a 4-year-old female with rapidly progressive developmental regression with loss of motor milestones, spasticity and dysphagia. MRI showed volume loss and markedly abnormal deep white matter. Enzymatic testing in one laboratory showed arylsulfatase A activity in their normal range. However, extraction of urine showed a large increase in sulfatide excretion in …

Early Progression Of Krabbe Disease In Patients With Symptom Onset Between 0 And 5 Months., Maria L. Beltran-Quintero, Nicholas A. Bascou, Michele D. Poe, David A. Wenger, Carlos A. Saavedra-Matiz, Matthew J. Nichols, Maria L. Escolar

Department of Neurology Faculty Papers

BACKGROUND: Krabbe disease is a rare neurological disorder caused by a deficiency in the lysosomal enzyme, β-galactocerebrosidase, resulting in demyelination of the central and peripheral nervous systems. If left without treatment, Krabbe disease results in progressive neurodegeneration with reduced quality of life and early death. The purpose of this prospective study was to describe the natural progression of early onset Krabbe disease in a large cohort of patients.

METHODS: Patients with early onset Krabbe disease were prospectively evaluated between 1999 and 2018. Data sources included diagnostic testing, parent questionnaires, standardized multidisciplinary neurodevelopmental assessments, and neuroradiological and neurophysiological tests.

RESULTS: We …

Hemi-Eses Associated With Agenesis Of The Corpus Callosum And Normal Cognition., Mahmoud Mohammadi, Safoura Kowkabi, Ali Akbar Asadi-Pooya, Reza Azizi Malamiri, Reza Shervin Badv

Department of Neurology Faculty Papers

• Corpus callosum plays the important role in bilateral synchronous expression of focal discharges of ESES.
• Sparing dominant hemisphere form continuous spike and slow waves during sleep accounts for normal cognitive scores.
• Early detection and treatment of ESES have a great impact on cognitive and language scores and final prognosis.

Combination Therapy With Fingolimod And Neural Stem Cells Promotes Functional Myelination, Yuan Zhang, Xin-Yu Lu, Ze-Qin Ye, Bogoljub Ciric, Cun-Gen Ma, A. M. Rostami, Xing Li, Guang-Xian Zhang

Department of Neurology Faculty Papers

Myelination, which occurs predominantly postnatally and continues throughout life, is important for proper neurologic function of the mammalian central nervous system (CNS). We have previously demonstrated that the combination therapy of fingolimod (FTY720) and transplanted neural stem cells (NSCs) had a significantly enhanced therapeutic effect on the chronic stage of experimental autoimmune encephalomyelitis, an animal model of CNS autoimmunity, compared to using either one of them alone. However, reduced disease severity may be secondary to the immunomodulatory effects of FTY720 and NSCs, while whether this therapy directly affects myelinogenesis remains unknown. To investigate this important question, we used three myelination …

Quantitative Clinical And Autoimmune Assessments In Stiff Person Syndrome: Evidence For A Progressive Disorder., Goran Rakocevic, Harry Alexopoulos, Marinos C. Dalakas

Department of Neurology Faculty Papers

BACKGROUND: Stiff Person Syndrome (SPS) is an under-diagnosed disorder that affects mobility and the quality of life of affected patients. The aim of the study is to describe the natural history of SPS, the extent of accumulated disability and the associated clinical and immunological features in patients followed for up to 8 years in a single center.

METHODS: Our collective cohort included 57 SPS patients. Additionally, 32 of these patients were examined every 6 months for a two-year period in a longitudinal study protocol, to assess disease progression using quantitative measures of stiffness and heightened sensitivity.

RESULTS: The most frequent …

Randomized Trial Of Polychromatic Blue-Enriched Light For Circadian Phase Shifting, Melatonin Suppression, And Alerting Responses., J. P. Hanifin, S. W. Lockley, K. Cecil, K. West, M. Jablonski, B. Warfield, M. James, M. Ayers, B. Byrne, E. Gerner, C. Pineda, M. Rollag, G. C. Brainard

Department of Neurology Faculty Papers

Wavelength comparisons have indicated that circadian phase-shifting and enhancement of subjective and EEG-correlates of alertness have a higher sensitivity to short wavelength visible light. The aim of the current study was to test whether polychromatic light enriched in the blue portion of the spectrum (17,000 K) has increased efficacy for melatonin suppression, circadian phase-shifting, and alertness as compared to an equal photon density exposure to a standard white polychromatic light (4000 K). Twenty healthy participants were studied in a time-free environment for 7 days. The protocol included two baseline days followed by a 26-h constant routine (CR1) to assess initial …

Genome-Wide Mega-Analysis Identifies 16 Loci And Highlights Diverse Biological Mechanisms In The Common Epilepsies., Bassel Abou-Khalil, Pauls Auce, Andreja Avbersek, Melanie Bahlo, David J. Balding, Thomas Bast, Larry Baum, Albert J. Becker, Felicitas Becker, Bianca Berghuis, Samuel F. Berkovic, Katja E. Boysen, Jonathan P. Bradfield, Lawrence C. Brody, Russell J. Buono, Ellen Campbell, Gregory D. Cascino, Claudia B. Catarino, Gianpiero L. Cavalleri, Stacey S. Cherny, Krishna Chinthapalli, Alison J. Coffey, Alastair Compston, Antonietta Coppola, Patrick Cossette, John J. Craig, Gerrit-Jan De Haan, Peter De Jonghe, Carolien G.F. De Kovel, Norman Delanty, Chantal Depondt, Orrin Devinsky, Dennis J. Dlugos, Colin P. Doherty, Christian E. Elger, Johan G. Eriksson, Thomas N. Ferraro, Martha Feuch, Ben Francis, Andre Franke, Jacqueline A. French, Saskia Freytag, Verena Gaus, Eric B. Geller, Christian Gieger, Tracy Glauser, Simon Glynn, David B. Goldstein, Hongsheng Gui, Youling Guo, Kevin F. Haas, Hakon Hakonarson, Kerstin Hallmann, Sheryl Haut, Erin L. Heinzen, Ingo Helbig, Christian Hengsbach, Helle Hjalgrim, Michele Iacomino, Andrés Ingason, Jennifer Jamnadas-Khoda, Michael R. Johnson, Reetta Kälviäinen, Anne-Mari Kantanen, Dalia Kasperavičiūte, Dorothee Kasteleijn-Nolst Trenite, Heidi E. Kirsch, Robert C. Knowlton, Bobby P.C. Koeleman, Roland Krause, Martin Krenn, Wolfram S. Kunz, Ruben Kuzniecky, Patrick Kwan, Dennis Lal, Yu-Lung Lau, Anna-Elina Lehesjoki, Holger Lerche, Costin Leu, Wolfgang Lieb, Dick Lindhout, Warren D. Lo, Iscia Lopes-Cendes, Daniel H. Lowenstein, Alberto Malovini, Anthony G. Marson, Thomas Mayer, Mark Mccormack, James L. Mills, Nasir Mirza, Martina Moerzinger, Rikke S. Møller, Anne M. Molloy, Hiltrud Muhle, Mark Newton, Ping-Wing Ng, Markus M. Nöthen, Peter Nürnberg, Terence J. O’Brien, Karen L. Oliver, Palotie Palotie, Faith Pangilinan, Sarah Peter, Slavé Petrovski, Annapurna Poduri, Michael Privitera, Rodney Radtke, Sarah Rau, Philipp S. Reif, Eva M. Reinthaler, Felix Rosenow, Josemir W. Sander, Thomas Sander, Theresa Scattergood, Steven C. Schachter, Christoph J. Schankin, Ingrid E. Scheffer, Bettina Schmitz, Susanne Schoch, Pak C. Sham, Jerry J. Shih, Graeme J. Sills, Sanjay M. Sisodiya, Lisa Slattery, Alexander Smith, David F. Smith, Michael C. Smith, Philip E. Smith, Anja C.M. Sonsma, Doug Speed, Michael R. Sperling, Bernhard J. Steinhoff, Ulrich Stephani, Remi Stevelink, Konstantin Strauch, Pasquale Striano, Hans Stroink, Rainer Surges, K. Meng Tan, Liu Lin Thio, G. Neil Thomas, Marian Todaro, Rossana Tozzi, Maria S. Vari, Ellen P.G. Vining, Frank Visscher, Sarah Von Spiczak, Nicole M. Walley, Yvonne G. Weber, Zhi Wei, Judith Weisenberg, Christopher D. Whelan, Peter Widdess-Walsh, Markus Wolff, Wolking Wolking, Wanling Yang, Federico Zara, Fritz Zimprich

Department of Neurology Faculty Papers

The epilepsies affect around 65 million people worldwide and have a substantial missing heritability component. We report a genome-wide mega-analysis involving 15,212 individuals with epilepsy and 29,677 controls, which reveals 16 genome-wide significant loci, of which 11 are novel. Using various prioritization criteria, we pinpoint the 21 most likely epilepsy genes at these loci, with the majority in genetic generalized epilepsies. These genes have diverse biological functions, including coding for ion-channel subunits, transcription factors and a vitamin-B6 metabolism enzyme. Converging evidence shows that the common variants associated with epilepsy play a role in epigenetic regulation of gene expression in the …

Triggers, Protectors, And Predictors In Episodic Migraine., Michael J. Marmura

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: A wide variety of triggers prompt attacks in episodic migraine. Although experimental triggers such as glyceryl trinitrate reliably produce migraine, natural triggers are much less predictable and vary in importance between individuals. This review describes the most common triggers in episodic migraine and provides strategies for managing them in clinical practice.

RECENT FINDINGS: Multiple migraine attack triggers have been established based on patient surveys, diary studies, and clinical trials. Stress, menstrual cycle changes, weather changes, sleep disturbances, alcohol, and other foods are among the most common factors mentioned. Clinical studies have verified that fasting, premenstrual periods in …

Medial Temporal Lobe Functional Connectivity Predicts Stimulation-Induced Theta Power., E. A. Solomon, J. E. Kragel, R. Gross, B. Lega, M. R. Sperling, G. Worrell, S. A. Sheth, K. A. Zaghloul, B. C. Jobst, J. M. Stein, S. Das, R. Gorniak, C. S. Inman, S. Seger, D. S. Rizzuto, M. J. Kahana

Department of Neurology Faculty Papers

Focal electrical stimulation of the brain incites a cascade of neural activity that propagates from the stimulated region to both nearby and remote areas, offering the potential to control the activity of brain networks. Understanding how exogenous electrical signals perturb such networks in humans is key to its clinical translation. To investigate this, we applied electrical stimulation to subregions of the medial temporal lobe in 26 neurosurgical patients fitted with indwelling electrodes. Networks of low-frequency (5-13 Hz) spectral coherence predicted stimulation-evoked increases in theta (5-8 Hz) power, particularly when stimulation was applied in or adjacent to white matter. Stimulation tended …

Distinct Role Of Il-27 In Immature And Lps-Induced Mature Dendritic Cell-Mediated Development Of Cd4, Fang Zhou, Guang-Xian Zhang, A. M. Rostami

Department of Neurology Faculty Papers

Interleukin-27 (IL-27) plays an important role in regulation of anti-inflammatory responses and autoimmunity; however, the molecular mechanisms of IL-27 in modulation of immune tolerance and autoimmunity have not been fully elucidated. Dendritic cells (DCs) play a central role in regulating immune responses mediated by innate and adaptive immune systems, but regulatory mechanisms of DCs in CD4⁺ T cell-mediated immune responses have not yet been elucidated. Here we show that IL-27 treated mature DCs induced by LPS inhibit immune tolerance mediated by LPS-stimulated DCs. IL-27 treatment facilitates development of the CD4⁺ CD127⁺3G11⁺ regulatory T cell subset …

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 …

Bath-Related Headache, Aliza Kumpinsky, Stephanie J. Nahas

Department of Neurology Faculty Papers

PURPOSE OF REVIEW: The purpose of this review is to summarize the most up-to-date literature on bath-related headache, a rare disorder.

RECENT FINDINGS: Initially described in middle-aged Asian women, it is now reported in a wider demographic. More information is available about the pathophysiology of bath-related headache, including its classification as a subtype of reversible cerebral vasoconstriction syndrome (RCVS). Nimodipine can be effective in patients both with and without vasospasm. Bath-related headache is a rare form of thunderclap headache. Although its mechanism is still unclear, it is associated with vasospasm and RCVS. Controlled trials investigating the use of nimodipine and …

Neurological Complications Of Immune Checkpoint Inhibitors: What Happens When You 'Take The Brakes Off' The Immune System., Marinos Dalakas

Department of Neurology Faculty Papers

Patients with advanced malignancies treated with immune checkpoint inhibitors are at increased risk for developing immune-related neurological complications. It is a phenomenon of immunological twist when immunotherapy against co-stimulatory molecules activates previously normal T cells to kill tumor cells but, in so doing, the T cells become unrestrained, triggering other autoimmune diseases for which conventional immunotherapy is needed. The most common autoimmune neurological diseases, usually occurring within 2-12 weeks after immune checkpoint inhibitor initiation, include: inflammatory myopathies, myasthenia gravis, acute and chronic demyelinating polyradiculoneuropathies, vasculitic neuropathies, isolated cranial neuropathies, aseptic meningitis, autoimmune encephalitis, multiple sclerosis and hypophysitis. The neurological events …

Hypoglycemic, Hypolipidemic And Antioxidant Effects Of Iridoid Glycosides Extracted From: Corni Fructus: Possible Involvement Of The Pi3k-Akt/Pkb Signaling Pathway, Jiefang Kang, Chen Guo, Rodolfo Thome, Ning Yang, Yuan Zhang, Xing Li, Xiaoyan Cao

Department of Neurology Faculty Papers

Iridoid glycosides (CIG) are the major component of Corni fructus. In this work, we researched the antioxidative, hypoglycemic and lowering blood lipids effects of CIG on diabetic mice induced by a high-fat diet (HFD) and streptozotocin (STZ). Furthermore, to investigate the molecular mechanism of action, the phosphorylation and protein expression of phosphoinositide 3-kinase (PI3K) and its downstream proteins, such as insulin receptor (INSR), protein kinase B (Akt/PKB) and glucose transporter 4 (GLUT4) have been detected. The results showed that CIG significantly improved oral glucose tolerance in diabetic mice. Biochemical indices also revealed that CIG had a positive effect on lipid …

Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang

Department of Neurology Faculty Papers

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and reduced …

Enhanced Co-Registration Methods To Improve Intracranial Electrode Contact Localization., Walter A. Hinds, Amrit Misra, Michael R. Sperling, Ashwini Sharan, Joseph I. Tracy, Karen A. Moxon

Department of Neurology Faculty Papers

Background: Electrode contact locations are important when planning tailored brain surgeries to identify pathological tissue targeted for resection and conversely avoid eloquent tissue. Current methods employ trained experts to use neuroimaging scans that are manually co-registered and localize contacts within ~2 mm. Yet, the state of the art is limited by either the expertise needed for each type of intracranial electrode or the inter-modality co-registration which increases error, reducing accuracy. Patients often have a variety of strips, grids and depths implanted; therefore, it is cumbersome and time-consuming to apply separate localization methods for each type of electrode, requiring expertise across …

Fasudil In Combination With Bone Marrow Stromal Cells (Bmscs) Attenuates Alzheimer's Disease-Related Changes Through The Regulation Of The Peripheral Immune System., Jiezhong Yu, Yuqing Yan, Qingfang Gu, Gajendra Kumar, Hongqiang Yu, Yijin Zhao, Chunyun Liu, Ye Gao, Zhi Chai, Jasleen Chumber, Bao-Guo Xiao, Guang-Xian Zhang, Han-Ting Zhang, Yuqiang Jiang, Cun-Gen Ma

Department of Neurology Faculty Papers

Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease. Its mechanism is still not clear. Majority of research focused on the central nervous system (CNS) changes, while few studies emphasize on peripheral immune system modulation. Our study aimed to investigate the regulation of the peripheral immune system and its relationship to the severity of the disease after treatment in an AD model of APPswe/PSEN1dE9 transgenic (APP/PS1 Tg) mice. APP/PS1 Tg mice (8 months old) were treated with the ROCK-II inhibitor 1-(5-isoquinolinesulfonyl)-homo-piperazine (Fasudil) (intraperitoneal (i.p.) injections, 25 mg/kg/day), bone marrow stromal cells (BMSCs; caudal vein injections, 1 × 10