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https://www.readbyqxmd.com/read/28943274/gene-therapy-induced-antigen-specific-tregs-inhibit-neuro-inflammation-and-reverse-disease-in-a-mouse-model-of-multiple-sclerosis
#1
Geoffrey D Keeler, Sandeep Kumar, Brett Palaschak, Emily L Silverberg, David M Markusic, Noah T Jones, Brad E Hoffman
The devastating neurodegenerative disease multiple sclerosis (MS) could substantially benefit from an adeno-associated virus (AAV) immunotherapy designed to restore a robust and durable antigen-specific tolerance. However, developing a sufficiently potent and lasting immune-regulatory therapy that can intervene in ongoing disease is a major challenge and has thus been elusive. We addressed this problem by developing a highly effective and robust tolerance-inducing in vivo gene therapy. Using a pre-clinical animal model, we designed a liver-targeting gene transfer vector that expresses full-length myelin oligodendrocyte glycoprotein (MOG) in hepatocytes...
September 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28940692/dpff-1-transcription-factor-deficiency-causes-the-aberrant-activation-of-mpk-1-and-meiotic-defects-in-the-caenorhabditis-elegans-germline
#2
Emmanuel Villanueva-Chimal, Laura S Salinas, Laura P Fernández-Cardenas, Gabriela Huelgas-Morales, Alejandro Cabrera-Wrooman, Rosa E Navarro
The d4 family of transcription factors consists of three members in mammals. DPF1/neuro-d4 is expressed mainly in neurons and the peripheral nervous system, and is important for brain development. DPF2/requiem/ubi-d4 is expressed ubiquitously and presumably functions as an apoptotic factor, especially during the deprivation of trophic factors. DPF3/cer-d4 is expressed in neurons and in the heart, and is important for heart development and function in zebrafish. In Drosophila, there is only one member, dd4, whose function is still unknown, but it is expressed in many tissues and is particularly abundant in the brain of developing embryos and in adults...
September 23, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28935570/molecular-alterations-in-a-mouse-cardiac-model-of-friedreich-s-ataxia-an-impaired-nrf2-response-mediated-via-up-regulation-of-keap1-and-activation-of-the-gsk3%C3%AE-axis
#3
Amy Anzovino, Shannon Chiang, Bronwyn E Brown, Clare L Hawkins, Des R Richardson, Michael L-H Huang
Nuclear factor-erythroid 2-related factor-2 (Nrf2) is a master regulator of the anti-oxidant response. However, studies in models of Friedreich's ataxia (FA), a neuro- and cardio-degenerative disease associated with oxidative stress, reported decreased Nrf2 expression due to unknown mechanisms. Using a mouse conditional frataxin knockout (KO) model in the heart and skeletal muscle, we examined the Nrf2 pathway in these tissues. Frataxin KO results in fatal cardiomyopathy, while skeletal muscle was asymptomatic...
September 18, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28933618/novel-cns-drug-discovery-and-development-approach-model-based-integration-to-predict-neuro-pharmacokinetics-and-pharmacodynamics
#4
Elizabeth C M de Lange, Willem van den Brink, Yumi Yamamoto, Wilhelmus E A de Witte, Yin Cheong Wong
CNS drug development has been hampered by inadequate consideration of CNS pharmacokinetic (PK), pharmacodynamics (PD) and disease complexity (reductionist approach). Improvement is required via integrative model-based approaches. Areas covered: The authors summarize factors that have played a role in the high attrition rate of CNS compounds. Recent advances in CNS research and drug discovery are presented, especially with regard to assessment of relevant neuro-PK parameters. Suggestions for further improvements are also discussed...
September 21, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28933267/neonatal-plasticity-of-the-nociceptive-system-mechanisms-effects-and-treatment-of-repetitive-painful-procedures-during-nicu-admittance
#5
N J Van den Hoogen, J Patijn, D Tibboel, E A Joosten
INTRODUCTION: In Neonatal Intensive Care Unit (NICU), prematurely born infants undergo a range of skin breaking and painful procedures. At the same time, the spinal nociceptive system is in a sensitive developmental stage. Both neonatal repetitive painful procedures and their treatment can induce plasticity of the neonatal spinal nociceptive system, causing long-lasting alterations to pain processing and pain reactivity. METHODS: This review focuses on developmental processes related to the nociceptive network in the spinal dorsal horn and more specifically at mechanisms related to 1...
September 21, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28931265/diagnostic-and-interventional-optical-angioscopy-in-ex-vivo-carotid-arteries
#6
Luis E Savastano, Neeraj Chaudhary, Carlos Murga-Zamalloa, Michael Wang, Thomas Wang, B Gregory Thompson
BACKGROUND: Angioscopy - or endovascular endoscopy - is a catheter-based technique employing a flexible fiberoptic angioscope to directly visualize arterial lumen. Poor resolution and excessive stiffness of pre-existent angioscopes limited their use clinically. Recent advances resulted in novel fused optical fiber bundle angioscopes with improved flexibility and imaging resolution. Use of these devices in endovascular neurosurgery is still largely unexplored. OBJECTIVE: To evaluate image quality and feasibility of optical angioscopes for diagnostic and interventional neuro-angioscopy in carotid arteries of human cadavers...
February 1, 2017: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/28931248/validity-evidence-for-the-neuro-endoscopic-ventriculostomy-assessment-tool-nevat
#7
Gerben E Breimer, Faizal A Haji, Giuseppe Cinalli, Eelco W Hoving, James M Drake
BACKGROUND: Growing demand for transparent and standardized methods for evaluating surgical competence prompted the construction of the Neuro-Endoscopic Ventriculostomy Assessment Tool (NEVAT). OBJECTIVE: To provide validity evidence of the NEVAT by reporting on the tool's internal structure and its relationship with surgical expertise during simulation-based training. METHODS: The NEVAT was used to assess performance of trainees and faculty at an international neuroendoscopy workshop...
February 1, 2017: Operative Neurosurgery (Hagerstown, Md.)
https://www.readbyqxmd.com/read/28929392/preventing-early-bouncebacks-to-the-neurointensive-care-unit-a-retrospective-analysis-and-quality-improvement-pilot
#8
David G Coughlin, Monisha A Kumar, Neha N Patel, Rebecca L Hoffman, Scott E Kasner
BACKGROUND: Early unplanned readmissions of "bouncebacks" to intensive care units are a healthcare quality metric and result in higher mortality and greater cost. Few studies have examined bouncebacks to the neurointensive care unit (neuro-ICU), and we sought to design and implement a quality improvement pilot to reduce that rate. METHODS: First, we performed a retrospective chart review of 504 transfers to identify potential bounceback risk factors. Risk factors were assessed on the day of transfer by the transferring physician identifying patients as "high risk" or "low risk" for bounceback...
September 19, 2017: Neurocritical Care
https://www.readbyqxmd.com/read/28919451/biphasic-modulation-of-neuro-and-interrenal-steroidogenesis-in-juvenile-african-sharptooth-catfish-clarias-gariepinus-exposed-to-waterborne-di-2-ethylhexyl-phthalate
#9
Augustine Arukwe, Oju R Ibor, Aina O Adeogun
Receptor (i.e. genomic) and non-receptor (or non-genomic) effects of endocrine toxicology have received limited or almost non-existent attention for tropical species and regions. In the present study, we have evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) on neuro- and interrenal steroidogenesis of the African catfish (Clarias gariepinus) using molecular, immunochemical and physiological approaches. Juvenile fish (mean weight and length: 5.6±0.6g and 8.2±1.2cm, respectively), were randomly distributed into ten 120L rectangular glass tanks containing 60L of dechlorinated tap water, at 50 fish per exposure group...
September 14, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28913785/evolution-of-patient-reported-outcomes-and-their-role-in-multiple-sclerosis-clinical-trials
#10
REVIEW
Cindy J Nowinski, Deborah M Miller, David Cella
Patient-reported outcomes (PROs) are playing an increasing role in multiple sclerosis (MS) research and practice, and are essential for understanding the effects that MS and MS treatments have on patients' lives. PROs are captured directly from patients and include symptoms, function, health status, and health-related quality of life. In this article, we review different categories (e.g., generic, targeted, preference-based) of PRO measures and considerations in selecting a measure. The PROs included in MS clinical research have evolved over time, as have the measures used to assess them...
September 14, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28912251/neuro-immune-interaction-and-the-regulation-of-intestinal-immune-homeostasis
#11
Simon Verheijden, Guy E Boeckxstaens
Many essential gastrointestinal functions, including motility, secretion and blood flow are regulated by the autonomic nervous system (ANS), both through intrinsic enteric neurons and extrinsic (sympathetic and parasympathetic) innervation. Recently identified neuro-immune mechanisms, in particular the interplay between enteric neurons and muscularis macrophages, are now considered to be essential for fine-tuning peristalsis. These findings shed new light on how intestinal immune cells can support enteric nervous function...
September 14, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28903026/differential-expression-of-genes-in-fetal-brain-as-a-consequence-of-maternal-protein-deficiency-and-nematode-infection
#12
Manjurul Haque, Lisa M Starr, Kristine G Koski, Marilyn E Scott
Maternal dietary protein deficiency and gastrointestinal nematode infection during early pregnancy have negative impacts on both maternal placental gene expression and fetal growth in the mouse. Here we used next-generation RNA sequencing to test our hypothesis that maternal protein deficiency and/or nematode infection also alter the expression of genes in the developing fetal brain. Outbred pregnant CD1 mice were used in a 2×2 design with two levels of dietary protein (24% versus 6%) and two levels of infection (repeated sham versus Heligmosomoides bakeri beginning at gestation day 5)...
September 10, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28902842/the-neuropeptide-nmu-amplifies-ilc2-driven-allergic-lung-inflammation
#13
Antonia Wallrapp, Samantha J Riesenfeld, Patrick R Burkett, Raja-Elie E Abdulnour, Jackson Nyman, Danielle Dionne, Matan Hofree, Michael S Cuoco, Christopher Rodman, Daneyal Farouq, Brian J Haas, Timothy L Tickle, John J Trombetta, Pankaj Baral, Christoph S N Klose, Tanel Mahlakõiv, David Artis, Orit Rozenblatt-Rosen, Isaac M Chiu, Bruce D Levy, Monika S Kowalczyk, Aviv Regev, Vijay K Kuchroo
Type 2 innate lymphoid cells (ILC2s) both contribute to mucosal homeostasis and initiate pathologic inflammation in allergic asthma. However, the signals that direct ILC2s to promote homeostasis versus inflammation are unclear. To identify such molecular cues, we profiled mouse lung-resident ILCs using single-cell RNA sequencing at steady state and after in vivo stimulation with the alarmin cytokines IL-25 and IL-33. ILC2s were transcriptionally heterogeneous after activation, with subpopulations distinguished by expression of proliferative, homeostatic and effector genes...
September 21, 2017: Nature
https://www.readbyqxmd.com/read/28895591/development-of-drug-loaded-polymer-microcapsules-for-treatment-of-epilepsy
#14
Yu Chen, Qi Gu, Zhilian Yue, Jeremy M Crook, Simon E Moulton, Mark J Cook, Gordon G Wallace
Despite significant progress in developing new drugs for seizure control, epilepsy still affects 1% of the global population and is drug-resistant in more than 30% of cases. To improve the therapeutic efficacy of epilepsy medication, a promising approach is to deliver anti-epilepsy drugs directly to affected brain areas using local drug delivery systems. The drug delivery systems must meet a number of criteria, including high drug loading efficiency, biodegradability, neuro-cytocompatibility and predictable drug release profiles...
September 12, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28894299/dhea-inhibits-acute-microglia-mediated-inflammation-through-activation-of-the-trka-akt1-2-creb-jmjd3-pathway
#15
V I Alexaki, G Fodelianaki, A Neuwirth, C Mund, A Kourgiantaki, E Ieronimaki, K Lyroni, M Troullinaki, C Fujii, W Kanczkowski, A Ziogas, M Peitzsch, S Grossklaus, B Sönnichsen, A Gravanis, S R Bornstein, I Charalampopoulos, C Tsatsanis, T Chavakis
Dehydroepiandrosterone (DHEA) is the most abundant circulating steroid hormone in humans, produced by the adrenals, the gonads and the brain. DHEA was previously shown to bind to the nerve growth factor receptor, tropomyosin-related kinase A (TrkA), and to thereby exert neuroprotective effects. Here we show that DHEA reduces microglia-mediated inflammation in an acute lipopolysaccharide-induced neuro-inflammation model in mice and in cultured microglia in vitro. DHEA regulates microglial inflammatory responses through phosphorylation of TrkA and subsequent activation of a pathway involving Akt1/Akt2 and cAMP response element-binding protein...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28887978/neuro-differentiated-ntera2-cancer-stem-cells-encapsulated-in-alginate-beads-first-evidence-of-biological-functionality
#16
Ilaria Cacciotti, Claudia Ceci, Alessandra Bianco, Giuseppa Pistritto
The present communication investigates an application of alginate encapsulation technology to the differentiation of the embryonic cancer stem NTera2 cells (NT2) into dopamine-producing cells. The encapsulation of cells in polymeric beads allows their immune isolation and makes them eligible for transplantation, thus representing a promising biotech tool for the delivery of biologically active compounds to the brain. The polysaccharide alginate is one of the most commonly used material for this procedure since it is well tolerated by various tissues, including the brain...
December 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28880359/-a-young-boy-with-periodic-strange-behavior-and-hypersomnia-kleine-levin-syndrome
#17
F Dauwe, L Imeraj, K Dhondt
Kleine-Levin syndrome is a rare neuro-psychiatric disease. Most of the young patients are males who present with hypersomnia, cognitive dysfunction, altered perception, eating disorder (e.g. hyperphagia) or disinhibited behaviour (e.g. hypersexuality). Psychiatric symptoms such as apathy, delusions and hallucinations, depressed mood and compulsive behaviours also appear often and result frequently in a psychiatric referral. These symptoms, however, should be distinguished from those of psychiatric diseases as early as possible in order to ensure that patients do not receive the wrong treatment...
2017: Tijdschrift Voor Psychiatrie
https://www.readbyqxmd.com/read/28875850/pharmacological-aspects-of-neuro-immune-interactions
#18
Vadim V Tarasov, Nikita V Kudryashov, Vladimir N Chubarev, Tatiana S Kalinina, George E Barreto, Ghulam Md Ashraf, Gjumrakch Aliev
The use of systematic approach for the analysis of mechanism of action of drugs at different levels of biological organization of organism is an important task in experimental and clinical pharmacology for drug designing and increasing the efficacy and safety of drugs. The analysis of published data on pharmacological effects of psychotropic drugs possessing immunomodulatory and/or antiviral properties have shown a correlation between central effects of examined drugs associated with the impact on the processes of neurogenesis of mature brain and survival of neurons, and their ability to alter levels of key proinflammatory cytokines...
August 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28875328/-critical-consideration-of-the-european-association-for-neuro-oncology-eano-guideline-on-the-diagnosis-and-treatment-of-adult-astrocytic-and-oligodendroglial-gliomas
#19
Sophia Scharl, Christoph Straube, Bernhard Meyer, Friederike Schmidt-Graf, Stephanie E Combs
No abstract text is available yet for this article.
September 5, 2017: Strahlentherapie und Onkologie: Organ der Deutschen Röntgengesellschaft ... [et Al]
https://www.readbyqxmd.com/read/28874832/antibiotic-induced-perturbations-in-microbial-diversity-during-post-natal-development-alters-amyloid-pathology-in-an-aged-appswe-ps1%C3%AE-e9-murine-model-of-alzheimer-s-disease
#20
Myles R Minter, Reinhard Hinterleitner, Marlies Meisel, Can Zhang, Vanessa Leone, Xiaoqiong Zhang, Paul Oyler-Castrillo, Xulun Zhang, Mark W Musch, Xunuo Shen, Bana Jabri, Eugene B Chang, Rudolph E Tanzi, Sangram S Sisodia
Recent evidence suggests the commensal microbiome regulates host immunity and influences brain function; findings that have ramifications for neurodegenerative diseases. In the context of Alzheimer's disease (AD), we previously reported that perturbations in microbial diversity induced by life-long combinatorial antibiotic (ABX) selection pressure in the APPSWE/PS1ΔE9 mouse model of amyloidosis is commensurate with reductions in amyloid-β (Aβ) plaque pathology and plaque-localised gliosis. Considering microbiota-host interactions, specifically during early post-natal development, are critical for immune- and neuro-development we now examine the impact of microbial community perturbations induced by acute ABX exposure exclusively during this period in APPSWE/PS1ΔE9 mice...
September 5, 2017: Scientific Reports
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