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https://www.readbyqxmd.com/read/28350947/traumatic-spinal-cord-injury-repair-and-regeneration
#1
Christopher S Ahuja, Satoshi Nori, Lindsay Tetreault, Jefferson Wilson, Brian Kwon, James Harrop, David Choi, Michael G Fehlings
BACKGROUND: Traumatic spinal cord injuries (SCI) have devastating consequences for the physical, financial, and psychosocial well-being of patients and their caregivers. Expediently delivering interventions during the early postinjury period can have a tremendous impact on long-term functional recovery. PATHOPHYSIOLOGY: This is largely due to the unique pathophysiology of SCI where the initial traumatic insult (primary injury) is followed by a progressive secondary injury cascade characterized by ischemia, proapoptotic signaling, and peripheral inflammatory cell infiltration...
March 1, 2017: Neurosurgery
https://www.readbyqxmd.com/read/28338546/a-double-blind-placebo-controlled-pilot-study-of-riluzole-monotherapy-for-acute-bipolar-depression
#2
Lawrence T Park, Marc S Lener, Matthew Hopkins, Nicolas Iadorola, Rodrigo Machado-Vieira, Elizabeth Ballard, Allison Nugent, Carlos A Zarate
BACKGROUND: Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects...
March 23, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28331009/the-modulation-of-two-motor-behaviours-by-persistent-sodium-currents-in-xenopus-laevis-tadpoles
#3
Erik Svensson, Hugo Jeffreys, Wen-Chang Li
Persistent sodium currents (INaP) are common in neuronal circuitries and they have been implicated in several diseases like amyotrophic lateral sclerosis (ALS) and epilepsy. However, the role of INaP in the regulation of specific behaviours is still poorly understood. Here we have characterized INaP and investigated its role in the swimming and struggling behaviour of Xenopus tadpoles. INaP was identified in three groups of neurons, namely sensory Rohon-Beard neurons (RB neurons), descending interneurons (dINs), and non-dINs (neurons rhythmically active in swimming)...
March 22, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28322166/glutamate-modulating-drugs-as-a-potential-therapeutic-strategy-in-obsessive-compulsive-disorder
#4
Zoya Marinova, De-Maw Chuang, Naomi Fineberg
OBJECTIVE: Obsessive-compulsive disorder (OCD) is a mental disease commonly associated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the current study was to review the clinical evidence for therapeutic utility of glutamate-modulating drugs as an augmentation or monotherapy in OCD patients...
March 20, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28318897/efficacy-of-off-label-augmentation-in-unipolar-depression-a-systematic-review-of-the-evidence
#5
REVIEW
Julia Kleeblatt, Felix Betzler, Laura L Kilarski, Tom Bschor, Stephan Köhler
Treatment of unipolar depression with currently available antidepressants is still unsatisfactory. Augmentation with lithium or second generation antipsychotics is an established practice in non-responders to antidepressant monotherapy, but is also associated with a substantial non-response rate and with non-tolerance. Based on a systematic review of the literature, including meta-analyses, randomized controlled trials (RCTs), non-randomized comparative studies and case studies, off-label augmentation agents (administered in addition to an antidepressant, without FDA approval for treatment of MDD) were identified and evaluated regarding their efficacy using levels of evidence...
March 16, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28302022/glial-cell-a-potential-target-for-cellular-and-drug-based-therapy-in-various-cns-diseases
#6
Shakeeb Ahmed, Yasmin Sultana, Azka Gull, Tahir Khuroo, Mohd Aqil
Glial cells are integrated part of neurovascular unit of blood brain barrier (BBB). They undergo mitosis and mainly classified as astrocytes, oligodendrocytes, microglia, ependymal cells and nerve glial antigen 2 cells. Being a most versatile glial cell, astrocytes provide structural support to neurons, maintain brain homeostasis, take part in neuronal communication, and perform some housekeeping functions. Oligodendrocytes myelinate the neuronal axons for proper transmission of nerve impulse and microglia are brain immune cells...
March 16, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28237716/clostridium-perfringens-epsilon-toxin-induces-permanent-neuronal-degeneration-and-behavioral-changes
#7
Winston E Morris, Jorge Goldstein, Leandro M Redondo, Adriana Cangelosi, Patricia Geoghegan, Marcela Brocco, Fabián C Loidl, Mariano E Fernandez-Miyakawa
Clostridium perfringens epsilon toxin (ETX), the most potent toxin produced by this bacteria, plays a key role in the pathogenesis of enterotoxaemia in ruminants, causing brain edema and encephalomalacia. Studies of animals suffering from ETX intoxication describe severe neurological disorders that are thought to be the result of vasogenic brain edemas and indirect neuronal toxicity, killing oligodendrocytes but not astrocytes, microglia, or neurons in vitro. In this study, by means of intravenous and intracerebroventricular delivery of sub-lethal concentrations of ETX, the histological and ultrastructural changes of the brain were studied in rats and mice...
February 22, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28231291/osteosarcoma-cell-proliferation-and-survival-requires-mglur5-receptor-activity-and-is-blocked-by-riluzole
#8
Sally Liao, Yuleisy Ruiz, Hira Gulzar, Zarina Yelskaya, Lyes Ait Taouit, Murielle Houssou, Trisha Jaikaran, Yuriy Schvarts, Kristina Kozlitina, Upal Basu-Roy, Alka Mansukhani, Shahana S Mahajan
Osteosarcomas are malignant tumors of bone, most commonly seen in children and adolescents. Despite advances in modern medicine, the poor survival rate of metastatic osteosarcoma has not improved in two decades. In the present study we have investigated the effect of Riluzole on a human and mouse metastatic osteosarcoma cells. We show that LM7 cells secrete glutamate in the media and that mGluR5 receptors are required for the proliferation of LM7 cells. Riluzole, which is known to inhibit glutamate release, inhibits proliferation, induces apoptosis and prevents migration of LM7 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28197100/rho-kinase-inhibition-with-fasudil-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis-symptomatic-treatment-potential-after-disease-onset
#9
René Günther, Alexander Balck, Jan C Koch, Tobias Nientiedt, Michael Sereda, Mathias Bähr, Paul Lingor, Lars Tönges
Despite an improved understanding of the genetic background and the pathomechanisms of amyotrophic lateral sclerosis (ALS) no novel disease-modifying therapies have been successfully implemented in clinical routine. Riluzole still remains the only clinically approved substance in human ALS treatment with limited efficacy. We have previously identified pharmacological rho kinase (ROCK) inhibitors as orally applicable substances in SOD1.G93A transgenic ALS mice (SOD1(G93A)), which are able to extend survival time and improve motor function after presymptomatic treatment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28194724/ketamine-and-beyond-investigations-into-the-potential-of-glutamatergic-agents-to-treat-depression
#10
REVIEW
Marc S Lener, Bashkim Kadriu, Carlos A Zarate
Clinical and preclinical studies suggest that dysfunction of the glutamatergic system is implicated in mood disorders such as major depressive disorder and bipolar depression. In clinical studies of individuals with major depressive disorder and bipolar depression, rapid reductions in depressive symptoms have been observed in response to subanesthetic-dose ketamine, an agent whose mechanism of action involves the modulation of glutamatergic signaling. The findings from these studies have prompted the repurposing and/or development of other glutamatergic modulators for antidepressant efficacy, both as monotherapy or as an adjunct to conventional monoaminergic antidepressants...
March 2017: Drugs
https://www.readbyqxmd.com/read/28193882/neuronal-hyperexcitability-in-a-mouse-model-of-scn8a-epileptic-encephalopathy
#11
Luis F Lopez-Santiago, Yukun Yuan, Jacy L Wagnon, Jacob M Hull, Chad R Frasier, Heather A O'Malley, Miriam H Meisler, Lori L Isom
Patients with early infantile epileptic encephalopathy (EIEE) experience severe seizures and cognitive impairment and are at increased risk for sudden unexpected death in epilepsy (SUDEP). EIEE13 [Online Mendelian Inheritance in Man (OMIM) # 614558] is caused by de novo missense mutations in the voltage-gated sodium channel gene SCN8A Here, we investigated the neuronal phenotype of a mouse model expressing the gain-of-function SCN8A patient mutation, p.Asn1768Asp (Nav1.6-N1768D). Our results revealed regional and neuronal subtype specificity in the effects of the N1768D mutation...
February 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28175531/329%C3%A2-efficacy-and-safety-of-riluzole-in-acute-spinal-cord-injury-rationale-and-design-of-aospine-phase-iii-multicenter-double-blinded-randomized-controlled-trial-riscis
#12
Michael G Fehlings, Branko Kopjar, Robert G Grossman
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28175502/321%C3%A2-development-of-intrathecal-riluzole-a-new-route-of-administration-for-the-treatment-of-amyotrophic-lateral-sclerosis-patients
#13
Juanmarco Gutierrez, Thais Federici, Bethany Peterson, Ray Bartus, Alexandre Betourne, Nicholas M Boulis
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28164143/a-predictive-model-for-prognosis-in-motor-neuron-disease
#14
Mirian Conceicao Moura, Luiz Augusto Casulari, Maria Rita Carvalho Garbi Novaes
OBJECTIVES: There have been attempts to establish biomarkers for motor neuron disease, without success. The study aim to seek possible markers to be used in the clinical routine evaluation, to optimize timing for palliative interventions. METHODS: A cohort study evaluated clinical, respiratory and neurophysiological variables every 3-4 months across 20 months in 101 patients with motor neuron disease using riluzole. Primary endpoint was death or tracheostomy. The most significant parameters in cox regression analysis created a predictive model...
December 2016: Journal of Neurological Disorders
https://www.readbyqxmd.com/read/28162597/-355-riluzole-actions-on-sk-channels-in-the-amygdala-in-acute-arthritic-and-chronic-neuropathic-pain
#15
J Thompson, G Ji, V Neugebauer
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28148632/serum-neurofilament-is-associated-with-progression-of-brain-atrophy-and-disability-in-early-ms
#16
Jens Kuhle, Bardia Nourbakhsh, Donna Grant, Steve Morant, Christian Barro, Özgür Yaldizli, Daniel Pelletier, Gavin Giovannoni, Emmanuelle Waubant, Sharmilee Gnanapavan
OBJECTIVE: To investigate a potential effect of riluzole on serum neurofilaments (Nf) compared to placebo and the relationship between longitudinal clinical and MRI outcomes and serum Nf levels. METHODS: Serum samples were obtained from participants enrolled in a randomized double-blind trial of neuroprotection with riluzole vs placebo as an add-on to weekly interferon-β (IFN-β)-1a IM initiated 3 months after randomization. Nf measurements were performed by ELISA and electrochemiluminescence immunoassay...
February 28, 2017: Neurology
https://www.readbyqxmd.com/read/28129947/target-intestinal-microbiota-to-alleviate-disease-progression-in-amyotrophic-lateral-sclerosis
#17
Yong-Guo Zhang, Shaoping Wu, Jianxun Yi, Yinglin Xia, Dapeng Jin, Jingsong Zhou, Jun Sun
PURPOSE: Emerging evidence has demonstrated that gut microbiome plays essential roles in the pathogenesis of human diseases in distal organs. Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons. Treatment with the only drug approved by the US Food and Drug Administration for use in ALS, riluzole, extends a patient׳s life span by only a few months. Thus, there is an urgent need to develop novel interventions that for alleviate disease progression and improve quality of life in patients with ALS...
February 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28095499/treatment-with-riluzole-restores-normal-control-of-soleus-and-extensor-digitorum-longus-muscles-during-locomotion-in-adult-rats-after-sciatic-nerve-crush-at-birth
#18
Wojciech Zmysłowski, Anna M Cabaj, Urszula Sławińska
The effects of sciatic nerve crush (SNC) and treatment with Riluzole on muscle activity during unrestrained locomotion were identified in an animal model by analysis of the EMG activity recorded from soleus (Sol) and extensor digitorum longus (EDL) muscles of both hindlimbs; in intact rats (IN) and in groups of rats treated for 14 days with saline (S) or Riluzole (R) after right limb nerve crush at the 1st (1S and 1R) or 2nd (2S and 2R) day after birth. Changes in the locomotor pattern of EMG activity were correlated with the numbers of survived motor units (MUs) identified in investigated muscles...
2017: PloS One
https://www.readbyqxmd.com/read/28072907/symptomatic-treatments-for-amyotrophic-lateral-sclerosis-motor-neuron-disease
#19
REVIEW
Louisa Ng, Fary Khan, Carolyn A Young, Mary Galea
BACKGROUND: Motor neuron disease (MND), which is also known as amyotrophic lateral sclerosis (ALS), causes a wide range of symptoms but the evidence base for the effectiveness of the symptomatic treatment therapies is limited. OBJECTIVES: To summarise the evidence from Cochrane Systematic Reviews of all symptomatic treatments for MND. METHODS: We searched the Cochrane Database of Systematic Reviews (CDSR) on 15 November 2016 for systematic reviews of symptomatic treatments for MND...
January 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28060747/25-hydroxycholesterol-is-involved-in-the-pathogenesis-of-amyotrophic-lateral-sclerosis
#20
Sung-Min Kim, Min-Young Noh, Heejaung Kim, So-Young Cheon, Kang Mi Lee, Jaeick Lee, Eunju Cha, Kyung Seok Park, Kwang-Woo Lee, Jung-Joon Sung, Seung Hyun Kim
This study aimed to evaluate the levels of three major hydroxycholesterols (24-, 25-, and 27-hydroxycholesterols) in the serum and cerebrospinal fluid (CSF) of patients with amyotrophic lateral sclerosis (ALS), as well as to show their role in the pathogenesis of ALS experimental models. The level of 25-hydroxycholesterol were higher in untreated ALS patients (n = 30) than in controls without ALS (n = 33) and ALS patients treated with riluzole (n = 9) both in their serum and CSF. The level of 25-hydroxycholesterol in the serum of ALS patients were significantly associated with their disease severity and rate of progression...
January 2, 2017: Oncotarget
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