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Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics

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https://www.readbyqxmd.com/read/30242774/can-arginase-inhibitors-be-the-answer-to-therapeutic-challenges-in-alzheimer-s-disease
#1
Saak Victor Ovsepian, Valerie Bríd O'Leary
While the extensive hunt for therapeutics combating Alzheimer's disease (AD) has fallen short of delivering effective treatments, breakthroughs towards understanding the disease mechanisms and identifying areas for future research have nevertheless been enabled. The majority of clinical trials with β- and γ-secretase modulators have been suspended from additional studies or terminated due to toxicity issues and health concerns. The lack of progress in developing innovative AD therapies has also prompted a resurgence of interest in more traditional symptomatic treatments with cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists, as well as in the research of immune response modulators...
September 21, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30232718/directional-deep-brain-stimulation
#2
REVIEW
Frank Steigerwald, Cordula Matthies, Jens Volkmann
Over the last years, deep brain stimulation has seen many technological innovations. New electrode designs allowing to direct the current flow not only in the vertical but also in the horizontal plane are the most recent. We summarize the concept of "directional deep brain stimulation" with its opportunities and challenges and the available study data and discuss the use of imaging techniques to assist programming deep brain stimulation devices.
September 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30225791/evaluation-of-3k3a-activated-protein-c-to-treat-neonatal-hypoxic-ischemic-brain-injury-in-the-spiny-mouse
#3
Stacey J Ellery, Madeleine G Goss, Nadine Brew, Hayley Dickinson, Nadia Hale, Domenic A LaRosa, David W Walker, Flora Y Wong
Neonatal hypoxic ischemic encephalopathy (HIE) resulting from intrapartum asphyxia is a global problem that causes severe disabilities and up to 1 million deaths annually. A variant form of activated protein C, 3K3A-APC, has cytoprotective properties that attenuate brain injury in models of adult stroke. In this study, we compared the ability of 3K3A-APC and APC (wild-type (wt)) to attenuate neonatal brain injury, using the spiny mouse (Acomys cahirinus) model of intrapartum asphyxia. Pups were delivered at 38 days of gestation (term = 39 days), with an intrapartum hypoxic insult of 7...
September 17, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30225790/inhibition-of-mir-155-limits-neuroinflammation-and-improves-functional-recovery-after-experimental-traumatic-brain-injury-in-mice
#4
Rebecca J Henry, Sarah J Doran, James P Barrett, Victoria E Meadows, Boris Sabirzhanov, Bogdan A Stoica, David J Loane, Alan I Faden
Micro-RNAs (miRs) are short, noncoding RNAs that negatively regulate gene expression at the post-transcriptional level and have been implicated in the pathophysiology of secondary damage after traumatic brain injury (TBI). Among miRs linked to inflammation, miR-155 has been implicated as a pro-inflammatory factor in a variety of organ systems. We examined the expression profile of miR-155, following experimental TBI (controlled cortical impact) in adult male C57Bl/6 mice, as well as the effects of acute or delayed administration of a miR-155 antagomir on post-traumatic neuroinflammatory responses and neurological recovery...
September 17, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30225789/ketogenic-diets-for-adult-neurological-disorders
#5
Tanya J W McDonald, Mackenzie C Cervenka
The current review highlights the evidence supporting the use of ketogenic diet therapies in the management of a growing number of neurological disorders in adults. An overview of the scientific literature supporting posited mechanisms of therapeutic efficacy is presented including effects on neurotransmission, oxidative stress, and neuro-inflammation. The clinical evidence supporting ketogenic diet use in the management of adult epilepsy, malignant glioma, Alzheimer's disease, migraine headache, motor neuron disease, and other neurologic disorders is highlighted and reviewed...
September 17, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30218214/automatic-removal-of-false-connections-in-diffusion-mri-tractography-using-topology-informed-pruning-tip
#6
REVIEW
Fang-Cheng Yeh, Sandip Panesar, Jessica Barrios, David Fernandes, Kumar Abhinav, Antonio Meola, Juan C Fernandez-Miranda
Diffusion MRI fiber tracking provides a non-invasive method for mapping the trajectories of human brain connections, but its false connection problem has been a major challenge. This study introduces topology-informed pruning (TIP), a method that automatically identifies singular tracts and eliminates them to improve the tracking accuracy. The accuracy of the tractography with and without TIP was evaluated by a team of 6 neuroanatomists in a blinded setting to examine whether TIP could improve the accuracy...
September 14, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30215171/supranutritional-sodium-selenate-supplementation-delivers-selenium-to-the-central-nervous-system-results-from-a-randomized-controlled-pilot-trial-in-alzheimer-s-disease
#7
Barbara R Cardoso, Blaine R Roberts, Charles B Malpas, Lucy Vivash, Sila Genc, Michael M Saling, Patricia Desmond, Christopher Steward, Rodney J Hicks, Jason Callahan, Amy Brodtmann, Steven Collins, Stephen Macfarlane, Niall M Corcoran, Christopher M Hovens, Dennis Velakoulis, Terence J O'Brien, Dominic J Hare, Ashley I Bush
Insufficient supply of selenium to antioxidant enzymes in the brain may contribute to Alzheimer's disease (AD) pathophysiology; therefore, oral supplementation may potentially slow neurodegeneration. We examined selenium and selenoproteins in serum and cerebrospinal fluid (CSF) from a dual-dose 24-week randomized controlled trial of sodium selenate in AD patients, to assess tolerability, and efficacy of selenate in modulating selenium concentration in the central nervous system (CNS). A pilot study of 40 AD cases was randomized to placebo, nutritional (0...
September 13, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30194614/brain-machine-interfaces-for-vision-restoration-the-current-state-of-cortical-visual-prosthetics
#8
REVIEW
Soroush Niketeghad, Nader Pouratian
Loss of vision alters the day to day life of blind individuals and may impose a significant burden on their family and the economy. Cortical visual prosthetics have been shown to have the potential of restoring a useful degree of vision via stimulation of primary visual cortex. Due to current advances in electrode design and wireless power and data transmission, development of these prosthetics has gained momentum in the past few years and multiple sites around the world are currently developing and testing their designs...
September 7, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30159850/mitochondrial-modulation-by-dichloroacetate-reduces-toxicity-of-aberrant-glial-cells-and-gliosis-in-the-sod1g93a-rat-model-of-amyotrophic-lateral-sclerosis
#9
Laura Martínez-Palma, Ernesto Miquel, Valentina Lagos-Rodríguez, Luis Barbeito, Adriana Cassina, Patricia Cassina
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron (MN) degeneration and gliosis. Neonatal astrocytes obtained from the SOD1G93A rat model of ALS exhibit mitochondrial dysfunction and neurotoxicity that can be reduced by dichloroacetate (DCA), a metabolic modulator that has been used in humans, and shows beneficial effects on disease outcome in SOD1G93A mice. Aberrant glial cells (AbGC) isolated from the spinal cords of adult paralytic SOD1G93A rats exhibit highly proliferative and neurotoxic properties and may contribute to disease progression...
August 29, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30136253/inclusion-body-myositis-update-on-pathogenesis-and-treatment
#10
REVIEW
Elie Naddaf, Richard J Barohn, Mazen M Dimachkie
Inclusion body myositis is the most common acquired myopathy after the age of 50. It is characterized by progressive asymmetric weakness predominantly affecting the quadriceps and/or finger flexors. Loss of ambulation and dysphagia are major complications of the disease. Inclusion body myositis can be associated with cytosolic 5'-nucleotidase 1A antibodies. Muscle biopsy usually shows inflammatory cells surrounding and invading non-necrotic muscle fibers, rimmed vacuoles, congophilic inclusions, and protein aggregates...
August 22, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30120709/lncrna-pvt1-facilitates-tumorigenesis-and-progression-of-glioma-via-regulation-of-mir-128-3p-grem1-axis-and-bmp-signaling-pathway
#11
Chao Fu, Dongyuan Li, Xiaonan Zhang, Naijie Liu, Guonan Chi, Xingyi Jin
The current research was aimed at probing into the role of long noncoding RNA (lncRNA) PVT1 in the pathogenesis of glioma and the regulatory mechanism of PVT1/miR-128-3p/GREM1 network in glioma via regulation of the bone morphogenetic protein (BMP) signaling pathway. Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. Real-time quantitative polymerase chain reaction, Western blot, MTT assay, flow cytometry, migration and invasion assays, and xenograft tumor model were utilized to examine the influence of the lncRNA PVT1/miR-128-3p/GREM1 network on the biological functions of glioma cells...
August 17, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30117059/pompe-disease-from-basic-science-to-therapy
#12
REVIEW
Lara Kohler, Rosa Puertollano, Nina Raben
Pompe disease is a rare and deadly muscle disorder. As a clinical entity, the disease has been known for over 75 years. While an optimist might be excited about the advances made during this time, a pessimist would note that we have yet to find a cure. However, both sides would agree that many findings in basic science-such as the Nobel prize-winning discoveries of glycogen metabolism, the lysosome, and autophagy-have become the foundation of our understanding of Pompe disease. The disease is a glycogen storage disorder, a lysosomal disorder, and an autophagic myopathy...
August 16, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30112701/inhibition-of-myd88-signaling-skews-microglia-macrophage-polarization-and-attenuates-neuronal-apoptosis-in-the-hippocampus-after-status-epilepticus-in-mice
#13
Jin-Tao Liu, Sheng-Xi Wu, Hua Zhang, Fang Kuang
Inflammation is implicated in epileptogenesis. Activated microglia and macrophages (MG/MΦ) are found in the brains of patients with epilepsy-related diseases and animal models of epilepsy. It is not yet known how the MG/MΦ activation phenotype affects pathological changes in the brain after a single seizure. In this study, we had 2 main purposes: first, to characterize post-status epilepticus (SE) inflammation by tracking MG/MΦ polarization, and, second, to explore the role of an innate immune receptor adaptor protein, namely, myeloid differentiation primary response gene 88 (MyD88), in the induction of SE in a mouse model...
August 15, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30112700/early-treatment-with-quinidine-in-2-patients-with-epilepsy-of-infancy-with-migrating-focal-seizures-eimfs-due-to-gain-of-function-kcnt1-mutations-functional-studies-clinical-responses-and-critical-issues-for-personalized-therapy
#14
Robertino Dilena, Jacopo C DiFrancesco, Maria Virginia Soldovieri, Antonella Giacobbe, Paolo Ambrosino, Ilaria Mosca, Maria Albina Galli, Sophie Guez, Monica Fumagalli, Francesco Miceli, Dario Cattaneo, Francesca Darra, Elena Gennaro, Federico Zara, Pasquale Striano, Barbara Castellotti, Cinzia Gellera, Costanza Varesio, Pierangelo Veggiotti, Maurizio Taglialatela
Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare early-onset developmental epileptic encephalopathy resistant to anti-epileptic drugs. The most common cause for EIMFS is a gain-of-function mutation in the KCNT1 potassium channel gene, and treatment with the KCNT1 blocker quinidine has been suggested as a rational approach for seizure control in EIMFS patients. However, variable results on the clinical efficacy of quinidine have been reported. In the present study, we provide a detailed description of the clinical, genetic, in vitro, and in vivo electrophysiological profile and pharmacological responses to quinidine of 2 EIMFS unrelated patients with a heterozygous de novo KCNT1 mutation: c...
August 15, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30112699/marked-age-related-changes-in-brain-iron-homeostasis-in-amyloid-protein-precursor-knockout-mice
#15
Abdel A Belaidi, Adam P Gunn, Bruce X Wong, Scott Ayton, Ambili T Appukuttan, Blaine R Roberts, James A Duce, Ashley I Bush
Proteolytic cleavage of the amyloid precursor protein (APP) into the Aβ peptide has been an extensively researched mechanism for Alzheimer's disease, but the normal function of the protein is less understood. APP functions to regulate neuronal iron content by stabilizing the surface presentation of ferroportin-the only iron exporter channel of cells. The present study aims to quantify the contribution of APP to brain and peripheral iron by examining the lifetime impact on brain and liver iron levels in APP knockout mice...
August 15, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30066084/psychiatric-symptoms-in-refractory-epilepsy-during-the-first-year-after-surgery
#16
Sònia Ramos-Perdigués, Eva Baillés, Anna Mané, Mar Carreño, Antonio Donaire, Jordi Rumià, Nuria Bargalló, Teresa Boget, Xavier Setoain, Manuel Valdés, Luís Pintor
Psychiatric morbidity in drug-resistant epilepsy is frequent. Surgery is the best therapeutic alternative for treating seizures, but the current evidence concerning the effects of surgery on psychiatric disorders (PDs) is inconclusive. We aim to clarify surgery's role in long-term PDs. Using a prospective controlled study, we analyzed the psychopathologic outcomes of patients with drug-resistant epilepsy, comparing those who underwent surgery to those who did not due to not being suitable. Surgical candidates were paired (n = 84) with the immediately following nonsurgical candidates (n = 68)...
July 31, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30030698/decreased-concentration-of-irisin-is-associated-with-poor-functional-outcome-in-ischemic-stroke
#17
Wen-Jun Tu, Han-Cheng Qiu, Jian-Lei Cao, Qiang Liu, Xian-Wei Zeng, Ji-Zong Zhao
Irisin was discovered as a PGC-1a-activated messenger of myocytes that links sedentary lifestyle, obesity, and diabetes. In this study, we investigated the short-term prognostic value of early measurement of irisin concentration in 1530 Han Chinese patients with acute ischemic stroke (AIS) from three stroke centers. The subjects were the first-ever AIS patients who were hospitalized at three stroke centers during the period from January 2015 to December 2016. Clinical information and stroke severity were collected at admission...
July 20, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30027430/a-dendritic-cell-targeted-adenoviral-vector-facilitates-adaptive-immune-response-against-human-glioma-antigen-cmv-ie-and-prolongs-survival-in-a-human-glioma-tumor-model
#18
Julius W Kim, J Robert Kane, Wojciech K Panek, Jacob S Young, Aida Rashidi, Dou Yu, Deepak Kanojia, Tanwir Hasan, Jason Miska, Miguel A Gómez-Lim, Ilya V Ulasov, Irina V Balyasnikova, Atique U Ahmed, Derek A Wainwright, Maciej S Lesniak
Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body's most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization...
July 19, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30019308/the-limb-girdle-muscular-dystrophies-is-treatment-on-the-horizon
#19
REVIEW
Mary Lynn Chu, Ellen Moran
There has been an ever-expanding list of the Limb-Girdle Muscular Dystrophies (LGMD). There are currently 8 subtypes of autosomal dominant (AD) and 26 subtypes of autosomal recessive (AR) LGMD. Despite continued research efforts to conquer this group of genetic neuromuscular disease, patients continue to be treated symptomatically with the aim of prevention or addressing complications. Mouse models have been helpful in clarifying disease pathogenesis as well as strategizing pathways for treatment. Discoveries in translational research as well as molecular therapeutic approaches have kept clinicians optimistic that more promising clinical trials will lead the way to finding the cure for these devastating disorders...
July 17, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/30006767/targeting-the-neuromuscular-junction-in-als
#20
EDITORIAL
James Wymer, David R Borchelt
No abstract text is available yet for this article.
July 13, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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