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Jun Ren, Xiuqing Ding, John J Greer
Inhalation of capsaicin based sprays can cause central respiratory depression and lethal apneas. There are contradictory reports regarding the sites of capsaicin action. Further, an understanding of the neurochemical mechanisms underlying capsaicin-induced apneas and the development of pharmacological interventions are lacking. The main objectives were to perform a systematic study of the mechanisms of action of capsaicin-induced apneas and to provide insights relevant to pharmacological intervention. In vitro and in vivo rat and TRPV1-null mouse models were used to measure respiratory parameters and seizure-like activity in the presence of capsaicin and compounds that modulate glutamatergic neurotransmission...
October 6, 2016: American Journal of Respiratory Cell and Molecular Biology
Christopher D L Johnson, Anthony R D'Amato, Ryan J Gilbert
There is currently no cure for individuals with spinal cord injury (SCI). While many promising approaches are being tested in clinical trials, the complexity of SCI limits several of these approaches from aiding complete functional recovery. Several different categories of biomaterials are investigated for their ability to guide axonal regeneration, to deliver proteins or small molecules locally, or to improve the viability of transplanted stem cells. The purpose of this study is to provide a brief overview of SCI, present the different categories of biomaterial scaffolds that direct and guide axonal regeneration, and then focus specifically on electrospun fiber guidance scaffolds...
2016: Cells, Tissues, Organs
Paul Talman, Thi Duong, Steve Vucic, Susan Mathers, Svetha Venkatesh, Robert Henderson, Dominic Rowe, David Schultz, Robert Edis, Merrilee Needham, Richard Macdonnell, Pamela McCombe, Carol Birks, Matthew Kiernan
OBJECTIVE: To capture the clinical patterns, timing of key milestones and survival of patients presenting with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) within Australia. METHODS: Data were prospectively collected and were timed to normal clinical assessments. An initial registration clinical report form (CRF) and subsequent ongoing assessment CRFs were submitted with a completion CRF at the time of death. DESIGN: Prospective observational cohort study...
September 30, 2016: BMJ Open
Leonardo Lara-Valderrábano, Luisa Rocha, Emilio J Galván
Propylparaben (PPB) is an antimicrobial preservative widely used in food, cosmetics, and pharmaceutics. Virtual screening methodologies predicted anticonvulsant activity of PPB that was confirmed in vivo. Thus, we explored the effects of PPB on the excitability of hippocampal neurons by using standard patch clamp techniques. Bath perfusion of PPB reduced the fast-inactivating sodium current (INa) amplitude, causing a hyperpolarizing shift in the inactivation curve of the INa, and markedly delayed the sodium channel recovery from the inactivation state...
September 28, 2016: Neurotoxicology
Ginette Thibault-Halman, Carly S Rivers, Christopher Bailey, Eve Tsai, Brian Drew, Vanessa Noonan, Michael Fehlings, Marcel F Dvorak, Dilinuer Kuerban, Brian K Kwon, Sean Christie
Traumatic spinal cord injury (tSCI) represents a significant burden of illness, but is relatively uncommon and heterogeneous, making it challenging to achieve sufficient subject enrollment in clinical trials of therapeutic interventions for acute SCI. The Rick Hansen Spinal Cord Injury Registry (RHSCIR) is a national SCI Registry that enters SCI patients from acute-care centers across Canada. To predict the feasibility of conducting clinical trials of acute SCI within Canada, we have applied the inclusion/exclusion criteria of six previously conducted SCI trials to the RHSCIR dataset and generated estimates of how many Canadian individuals would theoretically have been eligible for enrollment in these studies...
September 14, 2016: Journal of Neurotrauma
Hyang Sook Seol, Sang Eun Lee, Joon Seon Song, Hye Yong Lee, Sojung Park, Inki Kim, Shree Ram Singh, Suhwan Chang, Se Jin Jang
Liver cancer is one of the common malignancies in many countries and an increasing cause of cancer death. Despite of that, there are few therapeutic options available with inconsistent outcome, raising a need for developing alternative therapeutic options. Through a drug repositioning screening, we identified and investigated the action mechanism of the Riluzole, an amyotrophic lateral sclerosis (ALS) drug, on hepatocellular carcinoma (HCC) therapy. Treatment of the Riluzole leads to a suppression of cell proliferation in liver primary cancer cells and cancer cell lines...
September 6, 2016: Cancer Letters
Ian A Clark, Bryce Vissel
The basic mechanism of the major neurodegenerative diseases, including neurogenic pain, needs to be agreed upon before rational treatments can be determined, but this knowledge is still in a state of flux. Most have agreed for decades that these disease states, both infectious and non-infectious, share arguments incriminating excitotoxicity induced by excessive extracellular cerebral glutamate. Excess cerebral levels of tumor necrosis factor (TNF) are also documented in the same group of disease states. However, no agreement exists on overarching mechanism for the harmful effects of excess TNF, nor, indeed how extracellular cerebral glutamate reaches toxic levels in these conditions...
2016: Journal of Neuroinflammation
Hosein Shamshiri, Farzad Fatehi, Roya Abolfazli, Mohammad Hossein Harirchian, Behnaz Sedighi, Babak Zamani, Ali Roudbari, Nazanin Razazian, Fatemeh Khamseh, Shahriar Nafissi
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an incurable progressive neurodegenerative disease and thus the assessment of quality of life (QOL) changes and factors that may influence its course is valuable in the meantime. OBJECTIVES: The present study aimed to assess the deterioration rate of QOL and influencing factors in different subgroups of Iranian ALS patients. METHODS: 132 patients were evaluated in this prospective multicenter observational study...
September 15, 2016: Journal of the Neurological Sciences
Alyssa N Calder, Elliot J Androphy, Kevin J Hodgetts
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease resulting from pathologically low levels of survival motor neuron (SMN) protein. The majority of mRNA from the SMN2 allele undergoes alternative splicing and excludes critical codons, causing an SMN protein deficiency. While there is currently no FDA-approved treatment for SMA, early therapeutic efforts have focused on testing repurposed drugs such as phenylbutyrate (2), valproic acid (3), riluzole (6), hydroxyurea (7), and albuterol (9), none of which has demonstrated clinical effectiveness...
August 16, 2016: Journal of Medicinal Chemistry
Shunya Nakane, Yuishin Izumi, Masaya Oda, Ryuji Kaji, Hidenori Matsuo
Objective Bullous pemphigoid in amyotrophic lateral sclerosis (BP-ALS) is rare and poorly understood. We herein assessed the association between ALS and BP using clinical and biological findings. Methods The clinical features of six new BP-ALS cases were described and collated with cases from a systematic literature review. Results Our six cases were combined with three other published cases. The mean disease duration (from ALS onset to the occurrence of BP) was 5.6±3.1 years. All patients had limb-onset ALS...
2016: Internal Medicine
Jahangir Sajjad, Valeria D Felice, Anna V Golubeva, John F Cryan, Siobhain M O'Mahony
Females are more likely to experience visceral pain than males, yet mechanisms underlying this sex bias are not fully elucidated. Moreover, pain sensitivity can change throughout the menstrual cycle. Alterations in the glutamatergic system have been implicated in several pain-disorders; however, whether these are sex-dependent is unclear. Thus, we aimed to investigate sex differences in the spinal cord glutamate uptake and how it varies across the estrous cycle. The activity of the glutamate transporters, excitatory amino acid transporters (EAATs) was assessed using an ex vivo aspartate radioactive uptake assay in the lumbosacral spinal cord in Sprague-Dawley male and female rats...
October 1, 2016: Neuroscience
Alexander McGown, Dame Pamela J Shaw, Tennore Ramesh
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease with death on average within 2-3 years of symptom onset. Mutations in superoxide dismutase 1 (SOD1) have been identified to cause ALS. Riluzole, the only neuroprotective drug for ALS provides life extension of only 3 months on average. Thishighlights the need for compound screening in disease models to identify new neuroprotective therapies for this disease. Zebrafish is an emerging model system that is well suited for the study of diseasepathophysiology and also for high throughput (HT) drug screening...
2016: Molecular Neurodegeneration
Thanuja Dharmadasa, José M Matamala, Matthew C Kiernan
PURPOSE OF REVIEW: Although there is no cure for motor neurone disease (MND), the advent of multidisciplinary care and neuroprotective agents has improved treatment interventions and enhanced quality of life for MND patients and their carers. RECENT FINDINGS: Evidence-based multidisciplinary care, respiratory management and disease-modifying therapy have improved the outcomes of patients diagnosed with MND. Supportive approaches to nutritional maintenance and optimization of symptomatic treatments, including management of communication and neuropsychiatric issues, improve the quality of life for MND patients...
October 2016: Current Opinion in Neurology
Yves Lecarpentier, Alexandre Vallée
The opposite interplay between peroxisome proliferator-activated receptor gamma (PPAR gamma) and Wnt/beta-catenin signaling has led to the categorization of neurodegenerative diseases (NDs) as either NDs in which PPAR gamma is downregulated while the canonical Wnt/beta-catenin pathway is upregulated [amyotrophic lateral sclerosis (ALS), Parkinson's disease, Huntington's disease, multiple sclerosis, Friedreich's ataxia] or NDs in which PPAR gamma is upregulated while the canonical Wnt/beta-catenin signaling is downregulated (bipolar disorder, schizophrenia, Alzheimer's disease)...
2016: Frontiers in Neurology
Cecilia Marini, Angelina Cistaro, Cristina Campi, Andrea Calvo, Claudia Caponnetto, Flavio Mariano Nobili, Piercarlo Fania, Mauro C Beltrametti, Cristina Moglia, Giovanni Novi, Ambra Buschiazzo, Annalisa Perasso, Antonio Canosa, Carlo Scialò, Elena Pomposelli, Anna Maria Massone, Maria Caludia Bagnara, Stefania Cammarosano, Paolo Bruzzi, Silvia Morbelli, Gianmario Sambuceti, Gianluigi Mancardi, Michele Piana, Adriano Chiò
PURPOSE: In amyotrophic lateral sclerosis, functional alterations within the brain have been intensively assessed, while progression of lower motor neuron damage has scarcely been defined. The aim of the present study was to develop a computational method to systematically evaluate spinal cord metabolism as a tool to monitor disease mechanisms. METHODS: A new computational three-dimensional method to extract the spinal cord from (18)F-FDG PET/CT images was evaluated in 30 patients with spinal onset amyotrophic lateral sclerosis and 30 controls...
October 2016: European Journal of Nuclear Medicine and Molecular Imaging
B Nourbakhsh, L Julian, E Waubant
BACKGROUND AND PURPOSE: The clinical predictors of health-related quality of life (HRQoL) in multiple sclerosis (MS) have mainly been studied in patients with long-standing disease. The objective of this study was to investigate the longitudinal association among HRQoL and clinical characteristics in early MS. METHODS: Relapsing MS patients within 12 months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo as an add-on to weekly interferon with up to 36 months of follow-up...
September 2016: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Marina De Tommaso, Miriam Kunz, Massimiliano Valeriani
INTRODUCTION Neurodegenerative diseases are increasing in parallel to the lengthening of survival. The management of Alzheimer's disease (AD) and other dementias, Parkinson's disease (PD) and PD-related disorders, and motor neuron diseases (MND), is mainly targeted to motor and cognitive impairment, with special care for vital functions such as breathing and feeding. AREAS COVERED The present review focuses on chronic pain in main neurodegenerative diseases, addressing current evidence on pain therapeutic management, pain frequency and clinical features, and possible pathophysiological mechanisms...
July 11, 2016: Expert Review of Neurotherapeutics
Michael G Fehlings, Branko Kopjar, Robert G Grossman
INTRODUCTION: There is convincing evidence from the preclinical realm that the pharmacologic agent riluzole attenuates certain aspects of the secondary injury cascade leading to diminished neurological tissue destruction in animal spinal cord injury (SCI) models. The safety and pharmacokinetic profile of riluzole have been studied in a multicenter pilot study in 36 patients. Efficacy of riluzole in acute human SCI has not been established. METHODS: This ongoing multi-center, international double-blinded phase III randomized controlled trial will enroll 351 patients with acute C4 C8 SCI and ASIA Impairment Grade A, B, or C randomly assigned 1:1 to riluzole and placebo...
August 2016: Neurosurgery
Juanmarco Gutierrez, Thais Federici, Bethany Peterson, Ray Bartus, Alexandre Betourne, Nicholas M Boulis
INTRODUCTION: Oral administration of riluzole is the only Food and Drug Administration-approved therapy for amyotrophic lateral sclerosis (ALS). However, per os riluzole therapy has shown modest efficacy and is limited by its negative impact on liver function. We hypothesize that intrathecal (IT) administration of riluzole will significantly improve drug efficacy by increasing local concentrations at targeted spinal cord segments, while circumventing peripheral toxicity. METHODS: A programmable infusion pump (SynchroMed II) connected to an IT catheter (Ascenda) was implanted into Göttingen minipigs to deliver a newly developed riluzole formulation...
August 2016: Neurosurgery
Jacob A Vincent, Krystyna B Wieczerzak, Hanna M Gabriel, Paul Nardelli, Mark M Rich, Timothy C Cope
Persistent neurotoxic side effects of oxaliplatin (OX) chemotherapy, including sensory ataxia, limit the efficacy of treatment and significantly diminish patient quality of life. The common explanation for neurotoxicity is neuropathy, however the degree of neuropathy varies greatly among patients and appears insufficient in some cases to fully account for disability. We recently identified an additional mechanism that might contribute to sensory ataxia following OX treatment. In the present study, we tested whether that mechanism, selective modification of sensory signaling by muscle proprioceptors might result in behavioral deficits in rats...
November 2016: Neurobiology of Disease
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