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Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics

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https://www.readbyqxmd.com/read/28194663/cilostazol-use-is-associated-with-reduced-risk-of-dementia-a-nationwide-cohort-study
#1
Shu-Yu Tai, Chen-Yu Chien, Yu-Han Chang, Yuan-Han Yang
Whether antiplatelet agents have a preventive effect on cognitive function remains unknown. We examined the potential association between the use of cilostazol, an antiplatelet agent and cyclic adenosine monophosphate phosphodiesterase 3 inhibitor, and the risk of dementia in an Asian population. Patients initiating cilostazol therapy between 1 January 2004 and 31 December 2009 without a prior history of dementia were identified from Taiwan's National Health Insurance database. Participants were stratified by age, sex, comorbidities, and comedication...
February 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28138837/donepezil-plus-solifenacin-cpc-201-treatment-for-alzheimer-s-disease
#2
Thomas N Chase, Martin R Farlow, Kathleen Clarence-Smith
Available cholinergic drugs for treating Alzheimer's disease (AD) provide modest symptomatic benefit. We hypothesized that co-administration of a peripheral anticholinergic to reduce dose-limiting adverse effects (AEs) would enable the safe/tolerable use of higher cholinesterase inhibitor doses and thus improve their antidementia efficacy. A modified single-blind, ascending-dose, phase IIa study of donepezil plus solifenacin (CPC-201) lasting 26 weeks was conducted in 41 patients with probable AD of moderate severity...
January 30, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28108885/modified-criteria-for-radiographic-response-assessment-in-glioblastoma-clinical-trials
#3
REVIEW
Benjamin M Ellingson, Patrick Y Wen, Timothy F Cloughesy
Radiographic endpoints including response and progression are important for the evaluation of new glioblastoma therapies. The current RANO criteria was developed to overcome many of the challenges identified with previous guidelines for response assessment, however, significant challenges and limitations remain. The current recommendations build on the strengths of the current RANO criteria, while addressing many of these limitations. Modifications to the current RANO criteria include suggestions for volumetric response evaluation, use contrast enhanced T1 subtraction maps to increase lesion conspicuity, removal of qualitative non-enhancing tumor assessment requirements, use of the post-radiation time point as the baseline for newly diagnosed glioblastoma response assessment, and "treatment-agnostic" response assessment rubrics for identifying pseudoprogression, pseudoresponse, and a confirmed durable response in newly diagnosed and recurrent glioblastoma trials...
January 20, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28097486/the-therapeutic-effectiveness-of-delayed-fetal-spinal-cord-tissue-transplantation-on-respiratory-function-following-mid-cervical-spinal-cord-injury
#4
Chia-Ching Lin, Sih-Rong Lai, Yu-Han Shao, Chun-Lin Chen, Kun-Ze Lee
Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury...
January 17, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28083806/new-directions-in-anti-angiogenic-therapy-for-glioblastoma
#5
REVIEW
Nancy Wang, Rakesh K Jain, Tracy T Batchelor
Anti-angiogenic therapy has become an important component in the treatment of many solid tumors given the importance of adequate blood supply for tumor growth and metastasis. Despite promising preclinical data and early clinical trials, anti-angiogenic agents have failed to show a survival benefit in randomized controlled trials of patients with glioblastoma. In particular, agents targeting vascular endothelial growth factor (VEGF) appear to prolong progression free survival, possibly improve quality of life, and decrease steroid usage, yet the trials to date have demonstrated no extension of overall survival...
January 12, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28083805/early-minocycline-and-late-fk506-treatment-improves-survival-and-alleviates-neuroinflammation-neurodegeneration-and-behavioral-deficits-in-prion-infected-hamsters
#6
Syed Zahid Ali Shah, Deming Zhao, Giulio Taglialatela, Sher Hayat Khan, Tariq Hussain, Haodi Dong, Mengyu Lai, Xiangmei Zhou, Lifeng Yang
Prion infections of the central nervous system (CNS) are characterized by initial reactive gliosis followed by overt neuronal death. Gliosis is likely to be caused initially by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP(Sc)) of the normal cellular prion protein (PrP(c)) in the brain. Proinflammatory cytokines and chemokines released by PrP(Sc)-activated glia and stressed neurons may also contribute directly or indirectly to the disease development by enhancing gliosis and inducing neurotoxicity...
January 12, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28070747/enhanced-bulbar-function-in-amyotrophic-lateral-sclerosis-the-nuedexta-treatment-trial
#7
Richard Smith, Erik Pioro, Kathleen Myers, Michael Sirdofsky, Kimberly Goslin, Gregg Meekins, Hong Yu, James Wymer, Merit Cudkowicz, Eric A Macklin, David Schoenfeld, Gary Pattee
The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, and salivation in patients with ALS. Sixty patients with amyotrophic lateral sclerosis (ALS) received either Nuedexta or placebo for 28 to 30 days, followed by a 10 to 15-day washout period. Subsequently, patients were switched to the opposite treatment arm for the remaining days of the trial. The primary endpoint was a reduction in the self-report Center for Neurologic Study Bulbar Function Scale (CNS-BFS) score...
January 9, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28070746/boundary-cap-neural-crest-stem-cells-promote-survival-of-mutant-sod1-motor-neurons
#8
Tanya Aggarwal, Jan Hoeber, Patrik Ivert, Svitlana Vasylovska, Elena N Kozlova
ALS is a devastating disease resulting in degeneration of motor neurons (MNs) in the brain and spinal cord. The survival of MNs strongly depends on surrounding glial cells and neurotrophic support from muscles. We previously demonstrated that boundary cap neural crest stem cells (bNCSCs) can give rise to neurons and glial cells in vitro and in vivo and have multiple beneficial effects on co-cultured and co-implanted cells, including neural cells. In this paper, we investigate if bNCSCs may improve survival of MNs harboring a mutant form of human SOD1 (SOD1(G93A)) in vitro under normal conditions and oxidative stress and in vivo after implantation to the spinal cord...
January 9, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28050710/the-copper-bis-thiosemicarbazone-complex-cu-ii-atsm-is-protective-against-cerebral-ischemia-through-modulation-of-the-inflammatory-milieu
#9
Mikko T Huuskonen, Qing-Zhang Tuo, Sanna Loppi, Hiramani Dhungana, Paula Korhonen, Lachlan E McInnes, Paul S Donnelly, Alexandra Grubman, Sara Wojciechowski, Katarina Lejavova, Yuriy Pomeshchik, Laura Periviita, Lotta Kosonen, Martina Giordano, Frederick R Walker, Rong Liu, Ashley I Bush, Jari Koistinaho, Tarja Malm, Anthony R White, Peng Lei, Katja M Kanninen
Developing new therapies for stroke is urgently needed, as this disease is the leading cause of death and disability worldwide, and the existing treatment is only available for a small subset of patients. The interruption of blood flow to the brain during ischemic stroke launches multiple immune responses, characterized by infiltration of peripheral immune cells, the activation of brain microglial cells, and the accumulation of immune mediators. Copper is an essential trace element that is required for many critical processes in the brain...
January 3, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28004273/occipital-nerve-field-transcranial-direct-current-stimulation-normalizes-imbalance-between-pain-detecting-and-pain-inhibitory-pathways-in-fibromyalgia
#10
Dirk De Ridder, Sven Vanneste
Occipital nerve field (OCF) stimulation with subcutaneously implanted electrodes is used to treat headaches, more generalized pain, and even failed back surgery syndrome via unknown mechanisms. Transcranial direct current stimulation (tDCS) can predict the efficacy of implanted electrodes. The purpose of this study is to unravel the neural mechanisms involved in global pain suppression, mediated by occipital nerve field stimulation, within the realm of fibromyalgia. Nineteen patients with fibromyalgia underwent a placebo-controlled OCF tDCS...
December 21, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27995437/toward-personalized-targeted-therapeutics-an-overview
#11
REVIEW
Shiao-Pei S Weathers, Mark R Gilbert
In neuro-oncology, there has been a movement towards personalized medicine, or tailoring treatment to the individual patient. Ideally, tumor and patient evaluations would lead to the selection of the best treatment (based on tumor characterization) and the right dosing schedule (based on patient characterization). The recent advances in the molecular analysis of glioblastoma have created optimism that personalized targeted therapy is within reach. Although our understanding of the molecular complexity of glioblastoma has increased over the years, the path to developing effective targeted therapeutic strategies is wrought with many challenges, as described in this review...
December 19, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27957719/development-of-improved-hdac6-inhibitors-as-pharmacological-therapy-for-axonal-charcot-marie-tooth-disease
#12
Veronick Benoy, Pieter Vanden Berghe, Matthew Jarpe, Philip Van Damme, Wim Robberecht, Ludo Van Den Bosch
Charcot-Marie-Tooth disease (CMT) is the most common inherited peripheral neuropathy, with an estimated prevalence of 1 in 2500. The degeneration of motor and sensory nerve axons leads to motor and sensory symptoms that progress over time and have an important impact on the daily life of these patients. Currently, there is no curative treatment available. Recently, we identified histone deacetylase 6 (HDAC6), which deacetylates α-tubulin, as a potential therapeutic target in axonal CMT (CMT2). Pharmacological inhibition of the deacetylating function of HDAC6 reversed the motor and sensory deficits in a mouse model for mutant "small heat shock protein B1" (HSPB1)-induced CMT2 at the behavioral and electrophysiological level...
December 12, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27928708/withania-somnifera-reverses-transactive-response-dna-binding-protein-43-proteinopathy-in-a-mouse-model-of-amyotrophic-lateral-sclerosis-frontotemporal-lobar-degeneration
#13
Kallol Dutta, Priyanka Patel, Reza Rahimian, Daniel Phaneuf, Jean-Pierre Julien
Abnormal cytoplasmic mislocalization of transactive response DNA binding protein 43 (TARDBP or TDP-43) in degenerating neurons is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous work suggested that nuclear factor kappa B (NF-κB) may constitute a therapeutic target for TDP-43-mediated disease. Here, we investigated the effects of root extract of Withania somnifera (Ashwagandha), an herbal medicine with anti-inflammatory properties, in transgenic mice expressing a genomic fragment encoding human TDP-43(A315T) mutant...
December 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27921261/attempting-to-compensate-for-reduced-neuronal-nitric-oxide-synthase-protein-with-nitrate-supplementation-cannot-overcome-metabolic-dysfunction-but-rather-has-detrimental-effects-in-dystrophin-deficient-mdx-muscle
#14
Cara A Timpani, Adam J Trewin, Vanesa Stojanovska, Ainsley Robinson, Craig A Goodman, Kulmira Nurgali, Andrew C Betik, Nigel Stepto, Alan Hayes, Glenn K McConell, Emma Rybalka
Duchenne muscular dystrophy arises from the loss of dystrophin and is characterized by calcium dysregulation, muscular atrophy, and metabolic dysfunction. The secondary reduction of neuronal nitric oxide synthase (nNOS) from the sarcolemma reduces NO production and bioavailability. As NO modulates glucose uptake, metabolism, and mitochondrial bioenergetics, we investigated whether an 8-week nitrate supplementation regimen could overcome metabolic dysfunction in the mdx mouse. Dystrophin-positive control (C57BL/10) and dystrophin-deficient mdx mice were supplemented with sodium nitrate (85 mg/l) in drinking water...
December 5, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27909976/erratum-to-regulation-of-caveolin-1-and-junction-proteins-by-bfgf-contributes-to-the-integrity-of-blood-spinal-cord-barrier-and-functional-recovery
#15
Li-Bing Ye, Xi-Chong Yu, Qing-Hai Xia, Ying Yang, Da-Qing Chen, Fenzan Wu, Xiao-Jie Wei, Xie Zhang, Bin-Bin Zheng, Xiao-Bing Fu, Hua-Zi Xu, Xiao-Kun Li, Jian Xiao, Hong-Yu Zhang
No abstract text is available yet for this article.
December 1, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28083811/abstracts-from-hsg-2016-discovering-our-future-the-23rd-annual-meeting-of-the-huntington-study-group-hsg
#16
(no author information available yet)
No abstract text is available yet for this article.
January 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28054328/magnetoencephalography-and-new-imaging-modalities-in-epilepsy
#17
REVIEW
Jessica Falco-Walter, Christian Owen, Mishu Sharma, Christopher Reggi, Mandy Yu, Travis R Stoub, Michael A Stein
The success of epilepsy surgery is highly dependent on correctly identifying the entire epileptogenic region. Current state-of-the-art for localizing the extent of surgically amenable areas involves combining high resolution three-dimensional magnetic resonance imaging (MRI) with electroencephalography (EEG) and magnetoencephalography (MEG) source modeling of interictal epileptiform activity. Coupling these techniques with newer quantitative structural MRI techniques, such as cortical thickness measurements, however, may improve the extent to which the abnormal epileptogenic region can be visualized...
January 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27995438/urate-as-a-marker-of-risk-and-progression-of-neurodegenerative-disease
#18
REVIEW
Sabrina Paganoni, Michael A Schwarzschild
Urate is a naturally occurring antioxidant whose levels are associated with reduced risk of developing Parkinson's disease (PD) and Alzheimer's disease. Urate levels are also associated with favorable progression in PD, amyotrophic lateral sclerosis, Huntington's disease, and multisystem atrophy. These epidemiological data are consistent with laboratory studies showing that urate exhibits neuroprotective effects by virtue of its antioxidant properties in several preclinical models. This body of evidence supports the hypothesis that urate may represent a shared pathophysiologic mechanism across neurodegenerative diseases...
January 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27933486/an-appraisal-of-novel-biomarkers-for-evaluating-and-monitoring-neurologic-diseases-editorial-introduction
#19
EDITORIAL
Jeremy M Shefner, Marwan N Sabbagh
No abstract text is available yet for this article.
January 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27933485/fluid-based-biomarkers-for-amyotrophic-lateral-sclerosis
#20
REVIEW
Lucas T Vu, Robert Bowser
Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease with no effective treatment. Drug development has been hampered by the lack of biomarkers that aid in early diagnosis, demonstrate target engagement, monitor disease progression, and can serve as surrogate endpoints to assess the efficacy of treatments. Fluid-based biomarkers may potentially address these issues. An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients...
January 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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