-
Selective Immunomodulatory and Neuroprotective Effects of a NOD2 Receptor Agonist on Mouse Models of Multiple Sclerosis Neurotherapeutics (IF 6.035) Pub Date : 2021-01-21 Adham Fani Maleki, Giulia Cisbani, Nataly Laflamme, Paul Prefontaine, Marie-Michele Plante, Joanie Baillargeon, Manu Rangachari, Jean Gosselin, Serge Rivest
The significance of monocytes has been demonstrated in multiple sclerosis (MS). One of the therapeutic challenges is developing medications that induce mild immunomodulation that is solely targeting specific monocyte subsets without affecting microglia. Muramyl dipeptide (MDP) activates the NOD2 receptor, and systemic MDP administrations convert Ly6Chigh into Ly6Clow monocytes. Here, we report selective
-
Reducing Events of Noncompliance in Neurology Human Subjects Research: the Effect of Human Subjects Research Protection Training and Site Initiation Visits Neurotherapeutics (IF 6.035) Pub Date : 2021-01-21 Matthew J. Gooden, Gina Norato, Sandra B. Martin, Avindra Nath, Lauren Reoma
In an effort to minimize protocol noncompliance in neurological research studies that can potentially compromise patient safety, delay completion of the study, and result in premature termination and added costs, we determined the effect of investigator trainings and site initiation visits (SIVs) on the occurrence of noncompliance events. Results of protocol audits conducted at the National Institute
-
Decreased Level of Exosomal miR-5121 Released from Microglia Suppresses Neurite Outgrowth and Synapse Recovery of Neurons Following Traumatic Brain Injury Neurotherapeutics (IF 6.035) Pub Date : 2021-01-21 Chengcheng Zhao, Yuefei Deng, Yi He, Xianjian Huang, Chuanfang Wang, Weiping Li
Activated microglia can suppress neurite outgrowth and synapse recovery in the acute stage following traumatic brain injury (TBI). However, the underlying mechanism has not been clearly elucidated. Exosomes derived from microglia have been reported to play a critical role in microglia-neuron interaction in healthy and pathological brains. Here, we aimed to investigate the role of microglia-derived
-
Novel Interactions Involving the Mas Receptor Show Potential of the Renin–Angiotensin system in the Regulation of Microglia Activation: Altered Expression in Parkinsonism and Dyskinesia Neurotherapeutics (IF 6.035) Pub Date : 2021-01-20 Rafael Rivas-Santisteban, Jaume Lillo, Ana Muñoz, Ana I. Rodríguez-Pérez, José Luís Labandeira-García, Gemma Navarro, Rafael Franco
The renin–angiotensin system (RAS) not only plays an important role in controlling blood pressure but also participates in almost every process to maintain homeostasis in mammals. Interest has recently increased because SARS viruses use one RAS component (ACE2) as a target-cell receptor. The occurrence of RAS in the basal ganglia suggests that the system may be targeted to improve the therapy of neurodegenerative
-
Transplantation of Human Neural Precursor Cells Reverses Syrinx Growth in a Rat Model of Post-Traumatic Syringomyelia Neurotherapeutics (IF 6.035) Pub Date : 2021-01-19 Ning Xu, Tingting Xu, Raymond Mirasol, Lena Holmberg, Per Henrik Vincent, Xiaofei Li, Anna Falk, Eirikur Benedikz, Emilia Rotstein, Åke Seiger, Elisabet Åkesson, Scott Falci, Erik Sundström
Posttraumatic syringomyelia (PTS) is a serious condition of progressive expansion of spinal cord cysts, affecting patients with spinal cord injury years after injury. To evaluate neural cell therapy to prevent cyst expansion and potentially replace lost neurons, we developed a rat model of PTS. We combined contusive trauma with subarachnoid injections of blood, causing tethering of the spinal cord
-
Persistently Gadolinium-Enhancing Lesion Is a Predictor of Poor Prognosis in NMOSD Attack: a Clinical Trial Neurotherapeutics (IF 6.035) Pub Date : 2021-01-19 Yun Xu, Yi Ren, Xindi Li, Wangshu Xu, Xinli Wang, Yunyun Duan, Yaou Liu, Xinghu Zhang, De-Cai Tian
Gadolinium (Gd)-contrast MRI for reliable detection of blood–brain barrier (BBB) breakdown is widely used in neuromyelitis optica spectrum disorder (NMOSD) attack. Nonetheless, little is known about the predictive role of gadolinium-enhancing lesion in prognosis of NMOSD attack. The aim of this work is to investigate the predictive value of persistently Gd-enhanced lesions to medium-term outcome after
-
Effect of Capsaicinoids on Neurophysiological, Biochemical, and Mechanical Parameters of Swallowing Function Neurotherapeutics (IF 6.035) Pub Date : 2021-01-15 Sonja Suntrup-Krueger, Paul Muhle, Isabella Kampe, Paula Egidi, Tobias Ruck, Frank Lenze, Michael Jungheim, Richard Gminski, Bendix Labeit, Inga Claus, Tobias Warnecke, Joachim Gross, Rainer Dziewas
Oropharyngeal dysphagia is prevalent in age-related neurological disorders presenting with impaired efficacy and safety of swallowing due to a loss of muscle force and sensory deficits. Stimulating the oropharynx with capsaicin that mediates Substance P release is an emerging pharmacological treatment option which needs further scientific evidence. Our aim was to comprehensively evaluate the effect
-
Pipeline Embolization Device for Intracranial Aneurysms in a Large Chinese Cohort: Complication Risk Factor Analysis Neurotherapeutics (IF 6.035) Pub Date : 2021-01-14 Huibin Kang, Yu Zhou, Bin Luo, Nan Lv, Hongqi Zhang, Tianxiao Li, Donglei Song, Yuanli Zhao, Sheng Guan, Aisha Maimaitili, Yunyan Wang, Wenfeng Feng, Yang Wang, Jieqing Wan, Guohua Mao, Huaizhang Shi, Xinjian Yang, Jianmin Liu
During intracranial aneurysm embolization with the Pipeline embolization device (PED), ischemic and hemorrhagic complications have been observed in cases among Western populations. The postmarket multicenter registry study on the embolization of intracranial aneurysms with the PED in China, i.e., the PLUS study, was performed to assess real-world predictors of complications and functional outcomes
-
Palliative Care for Parkinson’s Spectrum Disorders: an Emerging Approach Neurotherapeutics (IF 6.035) Pub Date : 2021-01-13 Maya Katz
Parkinson’s spectrum disorders (PSD) are neurodegenerative parkinsonian conditions that carry a tremendous symptom burden. Palliative care is an interdisciplinary medical specialty that focuses on improving quality of life for patients and caregivers affected by serious life-limiting illnesses, at any stage of disease. Research and clinical programs into this emerging therapeutic approach remain limited
-
Imaging Familial and Sporadic Neurodegenerative Disorders Associated with Parkinsonism Neurotherapeutics (IF 6.035) Pub Date : 2021-01-11 David J. Brooks
In this paper, the structural and functional imaging changes associated with sporadic and genetic Parkinson’s disease and atypical Parkinsonian variants are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed, and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression is debated. Imaging changes associated with
-
Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury Neurotherapeutics (IF 6.035) Pub Date : 2021-01-08 Benita Jin, Monzurul Alam, Alexa Tierno, Hui Zhong, Roland R. Roy, Yury Gerasimenko, Daniel C. Lu, V. Reggie Edgerton
Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity
-
Blocking the Spinal Fbxo3/CARM1/K + Channel Epigenetic Silencing Pathway as a Strategy for Neuropathic Pain Relief Neurotherapeutics (IF 6.035) Pub Date : 2021-01-07 Ming-Chun Hsieh, Yu-Cheng Ho, Cheng-Yuan Lai, Hsueh-Hsiao Wang, Po-Sheng Yang, Jen-Kun Cheng, Gin-Den Chen, Soo-Cheen Ng, An-Sheng Lee, Kuang-Wen Tseng, Tzer-Bin Lin, Hsien-Yu Peng
Many epigenetic regulators are involved in pain-associated spinal plasticity. Coactivator-associated arginine methyltransferase 1 (CARM1), an epigenetic regulator of histone arginine methylation, is a highly interesting target in neuroplasticity. However, its potential contribution to spinal plasticity–associated neuropathic pain development remains poorly explored. Here, we report that nerve injury
-
Current Concepts and Controversies in the Management of REM Sleep Behavior Disorder Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 E. Matar, S. J. McCarter, E. K. St Louis, S. J. G. Lewis
Rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by dream enactment and the loss of muscle atonia during REM sleep, known as REM sleep without atonia (RSWA). RBD can result in significant injuries, prompting patients to seek medical attention. However, in others, it may present only as non-violent behaviors noted as an incidental finding during polysomnography (PSG). RBD typically
-
Adjuvant High-Flow Normobaric Oxygen After Mechanical Thrombectomy for Anterior Circulation Stroke: a Randomized Clinical Trial Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Zhe Cheng, Xiaokun Geng, Yanna Tong, David Dornbos, Mohammed Hussain, Gary B. Rajah, Jie Gao, Linlin Ma, Fenghai Li, Huishan Du, Marc Fisher, Yuchuan Ding
Adjuvant neuroprotective therapies for acute ischemic stroke (AIS) have demonstrated benefit in animal studies, albeit without human translation. We investigated the safety and efficacy of high-flow normobaric oxygen (NBO) after endovascular recanalization in anterior circulation stroke. This is a prospective randomized controlled study. Eligible patients were randomized to receive high-flow NBO by
-
What Animal Models Can Tell Us About Long-Term Psychiatric Symptoms in Sepsis Survivors: a Systematic Review Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Felipe Dal-Pizzol, Gabriela Ferreira de Medeiros, Monique Michels, Aurélien Mazeraud, Fernando Augusto Bozza, Cristiane Ritter, Tarek Sharshar
Lower sepsis mortality rates imply that more patients are discharged from the hospital, but sepsis survivors often experience sequelae, such as functional disability, cognitive impairment, and psychiatric morbidity. Nevertheless, the mechanisms underlying these long-term disabilities are not fully understood. Considering the extensive use of animal models in the study of the pathogenesis of neuropsychiatric
-
Deferiprone Treatment in Aged Transgenic Tau Mice Improves Y-Maze Performance and Alters Tau Pathology Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Shalini S. Rao, Larissa Lago, Irene Volitakis, Jay J. Shukla, Gawain McColl, David I. Finkelstein, Paul A. Adlard
The accumulation of neurofibrillary tangles (NFTs), which is composed of abnormally hyperphosphorylated tau aggregates, is the classic neuropathology associated with cognitive dysfunction in tauopathies such as Alzheimer’s disease (AD). However, there is an emerging theory suggesting that dysregulation in cerebral iron may contribute to NFT formation. Iron is speculated to bind to tau and induce conformational
-
Treatment of Disorders of Tone and Other Considerations in Pediatric Movement Disorders Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Stephen R. Deputy, Ann H. Tilton
Pediatric movement disorders (PMDs) consist of a heterogeneous group of signs and symptoms caused by numerous neurological diseases. Different neurological disorders in children also share overlapping movement disorders making a diagnosis of the underlying cause of the movement disorder challenging. The similarity of the symptoms across multiple disease types suggests that there may be a final common
-
Guanabenz Sensitizes Glioblastoma Cells to Sunitinib by Inhibiting GADD34-Mediated Autophagic Signaling Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Kuo-Hao Ho, Yi-Ting Lee, Peng-Hsu Chen, Chwen-Ming Shih, Chia-Hsiung Cheng, Ku-Chung Chen
Limited therapeutic efficacy of temozolomide (TMZ) against glioblastomas highlights the importance of exploring new drugs for clinical therapy. Sunitinib, a multitargeted receptor tyrosine kinase inhibitor, is currently being tested as therapy for glioblastomas. Unfortunately, sunitinib still has insufficient activity to cure glioblastomas. Our aim was to determine the molecular mechanisms counteracting
-
Combination of Hydroxychloroquine and Indapamide Attenuates Neurodegeneration in Models Relevant to Multiple Sclerosis Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Dennis Brown, Dorsa Moezzi, Yifei Dong, Marcus Koch, V. Wee Yong
As the underlying pathophysiology of progressive forms of multiple sclerosis (MS) remains unclear, current treatment strategies are inadequate. Progressive MS is associated with increased oxidative stress and neuronal damage in lesions along with an extensive representation of activated microglia/macrophages. To target these disease mechanisms, we tested the novel combination of generic medications
-
A Novel Second-Generation EP2 Receptor Antagonist Reduces Neuroinflammation and Gliosis After Status Epilepticus in Rats Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Asheebo Rojas, Radhika Amaradhi, Avijit Banik, Chunxiang Jiang, JuanMartin Abreu-Melon, Sarah Wang, Raymond Dingledine, Thota Ganesh
Prostaglandin-E2 (PGE2), an important mediator of inflammation, achieves its functions via four different G protein–coupled receptors (EP1, EP2, EP3, and EP4). We previously demonstrated that the EP2 receptor plays a proinflammatory and neurodegenerative role after status epilepticus (SE). We recently developed TG8-260 as a second-generation highly potent and selective EP2 antagonist. Here, we investigate
-
Intranasal Allopregnanolone Confers Rapid Seizure Protection: Evidence for Direct Nose-to-Brain Delivery Neurotherapeutics (IF 6.035) Pub Date : 2021-01-06 Dorota Zolkowska, Chun-Yi Wu, Michael A. Rogawski
Allopregnanolone, a positive modulator of GABAA receptors with antiseizure activity, has potential in the treatment of seizure emergencies. Instillation of allopregnanolone in 40% sulfobutylether-β-cyclodextrin into the nose in mice rapidly elevated the seizure threshold in the timed intravenous pentylenetetrazol (ED50, 5.6 mg/kg), picrotoxin (ED50, 5.9 mg/kg), and bicuculline seizure tests. The effect
-
Neurodevelopmental Disorders Commonly Presenting with Sleep Disturbances Neurotherapeutics (IF 6.035) Pub Date : 2021-01-05 Althea Robinson Shelton, Beth Malow
There are multiple disorders of neurodevelopment that present with co-occurring sleep disturbances. Many of these neurodevelopmental disorders (NDD) include sleep disturbances in their diagnostic criteria. Neurobiological, genetic, and environmental factors overlap to cause different sleep disorders in individuals with NDD. Caregivers often present reporting either insomnia or hypersomnia, and based
-
Revisiting Brain Tuberous Sclerosis Complex in Rat and Human: Shared Molecular and Cellular Pathology Leads to Distinct Neurophysiological and Behavioral Phenotypes Neurotherapeutics (IF 6.035) Pub Date : 2021-01-04 Viera Kútna, Valerie B. O’Leary, Ehren Newman, Cyril Hoschl, Saak V. Ovsepian
Tuberous sclerosis complex (TSC) is a dominant autosomal genetic disorder caused by loss-of-function mutations in TSC1 and TSC2, which lead to constitutive activation of the mammalian target of rapamycin C1 (mTORC1) with its decoupling from regulatory inputs. Because mTORC1 integrates an array of molecular signals controlling protein synthesis and energy metabolism, its unrestrained activation inflates
-
Correction to: The Treatment of Sleep Dysfunction in Neurodegenerative Disorders Neurotherapeutics (IF 6.035) Pub Date : 2020-12-18 Zanna J. Voysey, Roger A. Barker, Alpar S. Lazar
A Correction to this paper has been published: https://doi.org/10.1007/s13311-020-00980-w
-
Differential Effects of Fingolimod and Natalizumab on B Cell Repertoires in Multiple Sclerosis Patients Neurotherapeutics (IF 6.035) Pub Date : 2020-11-30 M. C. Kowarik, D. Astling, G. Lepennetier, A. Ritchie, B. Hemmer, G. P. Owens, Jeffrey L. Bennett
Natalizumab and fingolimod are effective multiple sclerosis (MS) therapies that disrupt lymphocyte migration but have differential effects on B cell maturation and trafficking. We investigated their effects on peripheral blood (PB) and cerebrospinal fluid (CSF) B cell repertoires using next-generation deep sequencing. Paired CSF and PB B cell subsets (naïve, CD27+ memory, and CD27−IgD− double-negative
-
The Dysregulation of OGT/OGA Cycle Mediates Tau and APP Neuropathology in Down Syndrome Neurotherapeutics (IF 6.035) Pub Date : 2020-11-30 Ilaria Zuliani, Chiara Lanzillotta, Antonella Tramutola, Antonio Francioso, Sara Pagnotta, Eugenio Barone, Marzia Perluigi, Fabio Di Domenico
Protein O-GlcNAcylation is a nutrient-related post-translational modification that, since its discovery some 30 years ago, has been associated with the development of neurodegenerative diseases. As reported in Alzheimer’s disease (AD), flaws in the cerebral glucose uptake translate into reduced hexosamine biosynthetic pathway flux and subsequently lead to aberrant protein O-GlcNAcylation. Notably,
-
Positive Airway Pressure Therapy in Sleep-Disordered Breathing Neurotherapeutics (IF 6.035) Pub Date : 2020-11-23 Janna R. Raphelson, Kimberly Y. Kreitinger, Atul Malhotra
Obstructive sleep apnea (OSA) is a highly prevalent condition with major neurocognitive and cardiovascular health effects. Positive airway pressure (PAP) therapy prevents the collapse of the pharyngeal airway to improve hypoxemia, hypercapnia, and sleep fragmentation caused by OSA. While adherence to PAP therapy has been thought to be a barrier to use, consistent usage is likely much higher than commonly
-
Cannabidiol Modulates Behavioural and Gene Expression Alterations Induced by Spontaneous Cocaine Withdrawal Neurotherapeutics (IF 6.035) Pub Date : 2020-11-23 Ani Gasparyan, Francisco Navarrete, Marta Rodríguez-Arias, José Miñarro, Jorge Manzanares
The aim of this study was to evaluate the effects of cannabidiol (CBD) on the behavioural and gene expression changes in a new animal model of spontaneous cocaine withdrawal. For this purpose, male CD-1 mice were exposed to progressive increasing doses of cocaine for 12 days (15 to 60 mg/kg/day, i.p.), evaluating spontaneous cocaine withdrawal 6 h after the last cocaine administration. The effects
-
Nightmare Disorder and Isolated Sleep Paralysis Neurotherapeutics (IF 6.035) Pub Date : 2020-11-23 Ambra Stefani, Birgit Högl
Nightmare disorder and recurrent isolated sleep paralysis are rapid eye movement (REM) parasomnias that cause significant distress to those who suffer from them. Nightmare disorder can cause insomnia due to fear of falling asleep through dread of nightmare occurrence. Hyperarousal and impaired fear extinction are involved in nightmare generation, as well as brain areas involved in emotion regulation
-
BDNF rs6265 Variant Alters Outcomes with Levodopa in Early-Stage Parkinson’s Disease Neurotherapeutics (IF 6.035) Pub Date : 2020-11-19 D. Luke Fischer, Peggy Auinger, John L. Goudreau, Allyson Cole-Strauss, Karl Kieburtz, Jordan J. Elm, Mallory L. Hacker, P. David Charles, Jack W. Lipton, Barbara A. Pickut, Caryl E. Sortwell
Disease outcomes are heterogeneous in Parkinson’s disease and may be predicted by gene variants. This study investigated if the BDNF rs6265 single nucleotide polymorphism (SNP) is associated with differential outcomes with specific pharmacotherapy treatment strategies in the “NIH Exploratory Trials in PD Long-term Study 1” (NET-PD LS-1, n = 540). DNA samples were genotyped for the rs6265 SNP and others
-
Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments Neurotherapeutics (IF 6.035) Pub Date : 2020-11-19 Maria Jimena Salcedo-Arellano, Ana Maria Cabal-Herrera, Ruchi Harendra Punatar, Courtney Jessica Clark, Christopher Allen Romney, Randi J Hagerman
Autism spectrum disorders (ASD) are subdivided into idiopathic (unknown) etiology and secondary, based on known etiology. There are hundreds of causes of ASD and most of them are genetic in origin or related to the interplay of genetic etiology and environmental toxicology. Approximately 30 to 50% of the etiologies can be identified when using a combination of available genetic testing. Many of these
-
Chronic Toxoplasma gondii Infection Alleviates Experimental Autoimmune Encephalomyelitis by the Immune Regulation Inducing Reduction in IL-17A/Th17 Via Upregulation of SOCS3 Neurotherapeutics (IF 6.035) Pub Date : 2020-11-17 Do-Won Ham, Sang-Gyun Kim, Seung-Hwan Seo, Ji-Hun Shin, Sang Hyung Lee, Eun-Hee Shin
Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS), a demyelinating autoimmune disease caused by the infiltration of a harmful autoreactive Th1 and Th17 cells. To mitigate MS, which is impossible to cure with medication only, immunomodulatory interventions that prevent Th17 cell activation are ideal. The objective of the present study was to analyze the effect
-
Double-Binding Botulinum Molecule with Reduced Muscle Paralysis: Evaluation in In Vitro and In Vivo Models of Migraine Neurotherapeutics (IF 6.035) Pub Date : 2020-11-17 Anna P. Andreou, Charlotte Leese, Rosaria Greco, Chiara Demartini, Eve Corrie, Deniz Simsek, Anna Zanaboni, Ksenia Koroleva, Joseph O. Lloyd, Giorgio Lambru, Ciara Doran, Oleg Gafurov, Elizabeth Seward, Rashid Giniatullin, Cristina Tassorelli, Bazbek Davletov
With a prevalence of 15%, migraine is the most common neurological disorder and among the most disabling diseases, taking into account years lived with disability. Current oral medications for migraine show variable effects and are frequently associated with intolerable side effects, leading to the dissatisfaction of both patients and doctors. Injectable therapeutics, which include calcitonin gene–related
-
Approach to Cognitive Impairment in Parkinson’s Disease Neurotherapeutics (IF 6.035) Pub Date : 2020-11-17 Qiang Zhang, Georgina M. Aldridge, Nandakumar S. Narayanan, Steven W. Anderson, Ergun Y. Uc
Cognitive dysfunction is common in Parkinson’s disease (PD) and predicts poor clinical outcomes. It is associated primarily with pathologic involvement of basal forebrain cholinergic and prefrontal dopaminergic systems. Impairments in executive functions, attention, and visuospatial abilities are its hallmark features with eventual involvement of memory and other domains. Subtle symptoms in the premotor
-
Approaches to Disease Modification for Parkinson’s Disease: Clinical Trials and Lessons Learned Neurotherapeutics (IF 6.035) Pub Date : 2020-11-17 Albert Y. Hung, Michael A. Schwarzschild
Despite many clinical trials over the last three decades, the goal of demonstrating that a treatment slows the progression of Parkinson’s disease (PD) remains elusive. Research advances have shed new insight into cellular pathways contributing to PD pathogenesis and offer increasingly compelling therapeutic targets. Here we review recent and ongoing clinical trials employing novel strategies toward
-
Correction to: Huntington Study Group Abstracts 2020 Neurotherapeutics (IF 6.035) Pub Date : 2020-11-16
This erratum is to correct Huntington Study Group Abstracts.
-
Targeting the RNA-Binding Protein HuR Alleviates Neuroinflammation in Experimental Autoimmune Encephalomyelitis: Potential Therapy for Multiple Sclerosis Neurotherapeutics (IF 6.035) Pub Date : 2020-11-16 Vittoria Borgonetti, Maria Domenica Sanna, Laura Lucarini, Nicoletta Galeotti
Multiple sclerosis (MS) is a chronic autoimmune inflammatory and neurodegenerative disease of the central nervous system characterized by demyelination, axonal loss, and motor dysfunction. Activated microglia are associated with the destruction of myelin in the CNS. Activated microglia produce cytokines and proinflammatory factors, favoring neuroinflammation, myelin damage, and neuronal loss, and it
-
Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin Neurotherapeutics (IF 6.035) Pub Date : 2020-11-12 Emmanuelle A. D. Schindler, R. Andrew Sewell, Christopher H. Gottschalk, Christina Luddy, L. Taylor Flynn, Hayley Lindsey, Brian P. Pittman, Nicholas V. Cozzi, Deepak C. D’Souza
While anecdotal evidence suggests that select 5-hydroxytryptamine 2A (5-HT2A) receptor ligands, including psilocybin, may have long-lasting therapeutic effects after limited dosing in headache disorders, controlled investigations are lacking. In an exploratory double-blind, placebo-controlled, cross-over study, adults with migraine received oral placebo and psilocybin (0.143 mg/kg) in 2 test sessions
-
The Treatment of Sleep Dysfunction in Neurodegenerative Disorders Neurotherapeutics (IF 6.035) Pub Date : 2020-11-11 Zanna J. Voysey, Roger A. Barker, Alpar S. Lazar
Abstract Sleep dysfunction is highly prevalent across the spectrum of neurodegenerative conditions and is a key determinant of quality of life for both patients and their families. Mounting recent evidence also suggests that such dysfunction exacerbates cognitive and affective clinical features of neurodegeneration, as well as disease progression through acceleration of pathogenic processes. Effective
-
Sleep-Related Breathing Disorders: When CPAP Is Not Enough Neurotherapeutics (IF 6.035) Pub Date : 2020-11-04 Bernardo Selim, Kannan Ramar
Three decades ago, continuous positive airway pressure (CPAP) was introduced to treat obstructive sleep apnea (OSA). Shortly after, bilevel positive airway pressure devices (BPAP) that independently adjusted inspiratory and expiratory positive airway pressure were developed to treat complex sleep-related breathing disorders unresponsive to CPAP. Based on the bilevel positive airway pressure platform
-
Overcoming Barriers to Parkinson Disease Trial Participation: Increasing Diversity and Novel Designs for Recruitment and Retention Neurotherapeutics (IF 6.035) Pub Date : 2020-11-04 Pavan A. Vaswani, Thomas F. Tropea, Nabila Dahodwala
Parkinson disease (PD) is highly prevalent among neurodegenerative diseases, affecting a diverse patient population. Despite a general willingness of patients to participate in clinical trials, only a subset of patients enroll in them. Understanding the barriers to trial participation will help to alleviate this discrepancy and improve trial participation. Underrepresented minorities, older patients
-
Ethyl Pyruvate–Derived Transdifferentiation of Astrocytes to Oligodendrogenesis in Cuprizone-Induced Demyelinating Model Neurotherapeutics (IF 6.035) Pub Date : 2020-11-02 Yan He, Jun An, Jun-Jun Yin, Qiang Miao, Ruo-Xuan Sui, Qing-Xian Han, Zhi-Bin Ding, Jian-Jun Huang, Cun-Gen Ma, Bao-Guo Xiao
-
Blockers of Wnt3a, Wnt10a, or β-Catenin Prevent Chemotherapy-Induced Neuropathic Pain In Vivo Neurotherapeutics (IF 6.035) Pub Date : 2020-10-30 Hee Kee Kim, Jingi Bae, Sung Ho Lee, Seon-Hee Hwang, Min-Sik Kim, Moon Jong Kim, Sohee Jun, Chris L. Cervantes, Youn-Sang Jung, Seunghoon Back, Hangyeore Lee, Seung-Eun Lee, Patrick M. Dougherty, Sang-Won Lee, Jae-Il Park, Salahadin Abdi
Although chemotherapy is a key cancer treatment, many chemotherapeutic drugs produce chronic neuropathic pain, called chemotherapy-induced neuropathic pain (CINP), which is a dose-limiting adverse effect. To date, there is no medicine that prevents CINP in cancer patients and survivors. We determined whether blockers of the canonical Wnt signaling pathway prevent CINP. Neuropathic pain was induced
-
Gene and Cell-Based Therapies for Parkinson’s Disease: Where Are We? Neurotherapeutics (IF 6.035) Pub Date : 2020-10-30 Philip C. Buttery, Roger A. Barker
Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks
-
Surgical Treatment of Parkinson’s Disease: Devices and Lesion Approaches Neurotherapeutics (IF 6.035) Pub Date : 2020-10-28 Vibhash D. Sharma, Margi Patel, Svjetlana Miocinovic
Surgical treatments have transformed the management of Parkinson’s disease (PD). Therapeutic options available for the management of PD motor complications include deep brain stimulation (DBS), ablative or lesioning procedures (pallidotomy, thalamotomy, subthalamotomy), and dopaminergic medication infusion devices. The decision to pursue these advanced treatment options is typically done by a multidisciplinary
-
A Nitroalkene Benzoic Acid Derivative Targets Reactive Microglia and Prolongs Survival in an Inherited Model of ALS via NF-κB Inhibition Neurotherapeutics (IF 6.035) Pub Date : 2020-10-28 Sofía Ibarburu, Mariángeles Kovacs, Valentina Varela, Jorge Rodríguez-Duarte, Mariana Ingold, Paulina Invernizzi, Williams Porcal, Ana Paula Arévalo, Karen Perelmuter, Mariela Bollati-Fogolín, Carlos Escande, Gloria V. López, Peter King, Ying Si, Yuri Kwon, Carlos Batthyány, Luis Barbeito, Emiliano Trias
Motor neuron degeneration and neuroinflammation are the most striking pathological features of amyotrophic lateral sclerosis (ALS). ALS currently has no cure and approved drugs have only a modest clinically therapeutic effect in patients. Drugs targeting different deleterious inflammatory pathways in ALS appear as promising therapeutic alternatives. Here, we have assessed the potential therapeutic
-
α6GABA A Receptor Positive Modulators Alleviate Migraine-like Grimaces in Mice via Compensating GABAergic Deficits in Trigeminal Ganglia Neurotherapeutics (IF 6.035) Pub Date : 2020-10-27 Hung-Ruei Tzeng, Ming Tatt Lee, Pi-Chuan Fan, Daniel E. Knutson, Tzu-Hsuan Lai, Werner Sieghart, James Cook, Lih-Chu Chiou
Migraine is caused by hyperactivity of the trigeminovascular system, where trigeminal ganglia (TG) play an important role. This hyperactivity might originate from an underfunctional GABAergic system in TG. To investigate this possibility, we adapted a mouse model of migraine by inducing migraine-like grimaces in male mice via repeated injections of nitroglycerin (NTG, 10 mg/kg, i.p.), once every 2 days
-
Iron and Ferroptosis as Therapeutic Targets in Alzheimer’s Disease Neurotherapeutics (IF 6.035) Pub Date : 2020-10-27 Andrew Gleason, Ashley I. Bush
Alzheimer’s disease (AD), one of the most common neurodegenerative diseases worldwide, has a devastating personal, familial, and societal impact. In spite of profound investment and effort, numerous clinical trials targeting amyloid-β, which is thought to have a causative role in the disease, have not yielded any clinically meaningful success to date. Iron is an essential cofactor in many physiological
-
Treatment of Dystonia: Medications, Neurotoxins, Neuromodulation, and Rehabilitation Neurotherapeutics (IF 6.035) Pub Date : 2020-10-23 Ian O. Bledsoe, Aaron C. Viser, Marta San Luciano
Dystonia is a complex disorder with numerous presentations occurring in isolation or in combination with other neurologic symptoms. Its treatment has been significantly improved with the advent of botulinum toxin and deep brain stimulation in recent years, though additional investigation is needed to further refine these interventions. Medications are of critical importance in forms of dopa-responsive
-
Go-sha-jinki-Gan Alleviates Inflammation in Neurological Disorders via p38-TNF Signaling in the Central Nervous System Neurotherapeutics (IF 6.035) Pub Date : 2020-10-20 Shiying Jiang, Kousuke Baba, Tatsusada Okuno, Makoto Kinoshita, Chi-Jing Choong, Hideki Hayakawa, Hiroshi Sakiyama, Kensuke Ikenaka, Seiichi Nagano, Tsutomu Sasaki, Munehisa Shimamura, Yoshitaka Nagai, Keisuke Hagihara, Hideki Mochizuki
Go-sha-jinki-Gan (GJG) is a traditional Japanese herbal medicine. In clinical practice, GJG is effective against neuropathic pain and hypersensitivity induced by chemotherapy or diabetes. In our previous study using a chronic constriction injury mouse model, we showed that GJG inhibited microglia activation by suppressing the expression of tumor necrosis factor-α (TNF-α) and p38 mitogen-activated protein
-
Withaferin-A Treatment Alleviates TAR DNA-Binding Protein-43 Pathology and Improves Cognitive Function in a Mouse Model of FTLD Neurotherapeutics (IF 6.035) Pub Date : 2020-10-19 Sunny Kumar, Daniel Phaneuf, Jean-Pierre Julien
Withaferin-A, an active withanolide derived from the medicinal herbal plant Withania somnifera induces autophagy, reduces TDP-43 proteinopathy, and improves cognitive function in transgenic mice expressing mutant TDP-43 modelling FTLD. TDP-43 is a nuclear DNA/RNA-binding protein with cellular functions in RNA transcription and splicing. Abnormal cytoplasmic aggregates of TDP-43 occur in several neurodegenerative
-
Amnion-Derived Multipotent Progenitor Cells Suppress Experimental Optic Neuritis and Myelitis Neurotherapeutics (IF 6.035) Pub Date : 2020-10-16 Reas S. Khan, Ahmara G. Ross, Keirnan Willett, Kimberly Dine, Rick Banas, Larry R. Brown, Kenneth S. Shindler
The human amnion has been used for decades in wound healing, particularly burns. Amnion epithelial cells (AECs) have been the focus of extensive research based on their possible pluripotent differentiation ability. A novel, cultured cell population derived from AECs, termed human amnion–derived multipotent progenitor (AMP) cells, secrete numerous cytokines and growth factors that enhance tissue regeneration
-
Novel Analgesics with Peripheral Targets Neurotherapeutics (IF 6.035) Pub Date : 2020-10-15 Cosmin I. Ciotu, Michael J. M. Fischer
A limited number of peripheral targets generate pain. Inflammatory mediators can sensitize these. The review addresses targets acting exclusively or predominantly on sensory neurons, mediators involved in inflammation targeting sensory neurons, and mediators involved in a more general inflammatory process, of which an analgesic effect secondary to an anti-inflammatory effect can be expected. Different
-
The Pharmacogenetics of Rituximab: Potential Implications for Anti-CD20 Therapies in Multiple Sclerosis Neurotherapeutics (IF 6.035) Pub Date : 2020-10-14 Michael Zhong, Anneke van der Walt, Maria Pia Campagna, Jim Stankovich, Helmut Butzkueven, Vilija Jokubaitis
There are a broad range of disease-modifying therapies (DMTs) available in relapsing-remitting multiple sclerosis (RRMS), but limited biomarkers exist to personalise DMT choice. All DMTs, including monoclonal antibodies such as rituximab and ocrelizumab, are effective in preventing relapses and preserving neurological function in MS. However, each agent harbours its own risk of therapeutic failure
-
CREB Participates in Paclitaxel-Induced Neuropathic Pain Genesis Through Transcriptional Activation of Dnmt3a in Primary Sensory Neurons Neurotherapeutics (IF 6.035) Pub Date : 2020-10-13 Yong Yang, Jing Wen, Bixin Zheng, Shaogen Wu, Qingxiang Mao, Lingli Liang, Zhisong Li, Thomas Bachmann, Alex Bekker, Yuan-Xiang Tao
Chemotherapy-induced peripheral neuropathic pain (CIPNP) often occurs in cancer patients treated with antineoplastic drugs. Therapeutic management of CIPNP is very limited, at least in part due to the largely unknown mechanisms that underlie CIPNP genesis. Here, we showed that systemic administration of the chemotherapeutic drug paclitaxel significantly and time-dependently increased the levels of
-
Lentiviral Interleukin-10 Gene Therapy Preserves Fine Motor Circuitry and Function After a Cervical Spinal Cord Injury in Male and Female Mice Neurotherapeutics (IF 6.035) Pub Date : 2020-10-13 Jessica Y. Chen, Emily J. Fu, Paras R. Patel, Alexander J. Hostetler, Hasan A. Sawan, Kayla A. Moss, Sarah E. Hocevar, Aileen J. Anderson, Cynthia A. Chestek, Lonnie D. Shea
In mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading
-
Modulation of the Microbiome in Parkinson’s Disease: Diet, Drug, Stool Transplant, and Beyond Neurotherapeutics (IF 6.035) Pub Date : 2020-10-09 Ethan G. Brown, Samuel M. Goldman
The gastrointestinal microbiome is altered in Parkinson’s disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson’s disease, a condition elusive to disease-modifying therapy thus far. The gastrointestinal
-
Levistolide A Attenuates Alzheimer’s Pathology Through Activation of the PPARγ Pathway Neurotherapeutics (IF 6.035) Pub Date : 2020-10-09 Xiaodan Qu, Peipei Guan, Li Han, Zhanyou Wang, Xueshi Huang
-
Sleep Issues in Parkinson’s Disease and Their Management Neurotherapeutics (IF 6.035) Pub Date : 2020-10-07 José Rafael P. Zuzuárregui, Emmanuel H. During
Parkinson’s disease (PD) is an alpha-synucleinopathy that leads to prominent motor symptoms including tremor, bradykinesia, and postural instability. Nonmotor symptoms including autonomic, neurocognitive, psychiatric symptoms, and sleep disturbances are also seen frequently in PD. The impact of PD on sleep is related to motor and nonmotor symptoms, in addition to the disruption of the pathways regulating
-
Central Nervous System Targets: Inhibitory Interneurons in the Spinal Cord Neurotherapeutics (IF 6.035) Pub Date : 2020-10-07