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https://www.readbyqxmd.com/read/29925652/axonal-transport-enables-neuron-to-neuron-propagation-of-hcov-oc43
#1
Mathieu Dubé, Alain Le Coupanec, Alan H M Wong, James M Rini, Marc Desforges, Pierre J Talbot
Human coronaviruses (HCoV) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients, the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the CNS upon still unclear circumstances. HCoV-induced neuropathologies in human are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb, piriform cortex then brainstem...
June 20, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29924713/long-term-effects-of-direct-current-are-reproduced-by-intermittent-depolarization-of-myelinated-nerve-fibers
#2
Marcin Bączyk, Elzbieta Jankowska
Direct current (DC) potently increases the excitability of myelinated afferent fibers in the dorsal columns, both during DC polarization of these fibers and during a considerable (>1 hour) post-polarization period. The aim of the present study was to investigate whether similarly long-lasting changes in the excitability of myelinated nerve fibers in the dorsal columns may be evoked by field potentials following stimulation of peripheral afferents and by subthreshold epidurally applied current pulses...
June 20, 2018: Journal of Neurophysiology
https://www.readbyqxmd.com/read/29923318/intraspinal-serotonergic-signaling-suppresses-locomotor-activity-in-larval-zebrafish
#3
Jacob E Montgomery, Sarah Wahlstrom-Helgren, Timothy D Wiggin, Brittany M Corwin, Christina Lillesaar, Mark A Masino
Serotonin (5HT) is a modulator of many vital processes in the spinal cord (SC), such as production of locomotion. In the larval zebrafish, intraspinal serotonergic neurons (ISNs) are a source of spinal 5HT that, despite the availability of numerous genetic and optical tools, has not yet been directly shown to affect the spinal locomotor network. In order to better understand the functions of ISNs, we used a combination of strategies to investigate ISN development, morphology, and function. ISNs were optically isolated from one another by photoconverting Kaede fluorescent protein in individual cells, permitting morphometric analysis as they developed in vivo...
June 19, 2018: Developmental Neurobiology
https://www.readbyqxmd.com/read/29921170/-express-atf2-but-not-atf3-participates-in-the-maintenance-of-nerve-injury-induced-tactile-allodynia-and-thermal-hyperalgesia
#4
Ana Belen Salinas-Abarca, Isabel Velazquez-Lagunas, Urzula Franco-Enzastiga, Jorge Elias Torres-López, Hector Isaac Rocha-Gonzalez, Vinicio Granados-Soto
Transcription factors are proteins that modulate the transcriptional rate of target genes in the nucleus in response to extracellular or cytoplasmic signals. Activating transcription factors 2 (ATF2) and 3 (ATF3) respond to environmental signals and maintain cellular homeostasis. There is evidence that inflammation and nerve injury modulate ATF2 and ATF3 expression. However, the function of these transcription factors in pain is unknown. The purpose of this study was to investigate the contribution of ATF2 and ATF3 to nerve injury-induced neuropathic pain...
January 1, 2018: Molecular Pain
https://www.readbyqxmd.com/read/29916184/antibiotics-protect-against-eae-by-increasing-regulatory-and-anti-inflammatory-cells
#5
Hilary A Seifert, Gil Benedek, Ha Nguyen, Grant Gerstner, Ying Zhang, Gail Kent, Arthur A Vandenbark, Jürgen Bernhagen, Halina Offner
A seven day pretreatment course of an oral antibiotic cocktail (Ampicillin, Metronidazole, Neomycin Sulfate, and Vancomycin) was shown to induce changes in peripheral immune regulation and protect mice from signs of experimental autoimmune encephalomyelitis (EAE). To determine if a shorter course of antibiotic pretreatment could also protect the mice from EAE and induce regulatory immune cells, studies were conducted using the same oral antibiotic cocktail for three days. In addition, the CNS was examined to determine the effects of antibiotic pretreatment on EAE disease course and immune modulation within the affected tissue...
June 18, 2018: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29913894/evaluation-of-a-novel-chemokine-receptor-2-ccr2-antagonist-in-painful-diabetic-polyneuropathy
#6
Jarkko Kalliomäki, Bror Jonzon, Karin Huizar, Michael O'Malley, Anita Andersson, David M Simpson
Background and aims Preclinical data suggest that the chemokine receptor 2 (CCR2) is involved in the pathophysiology of neuropathic pain through modulation of neuronal excitability, synaptic transmission and activation of spinal cord microglia. CCR2-antagonists have shown to be effective in preclinical models of neuropathic pain. The aim of this study was to evaluate the analgesic efficacy, safety and tolerability of a novel CCR2-antagonist, AZD2423, in patients with painful diabetic neuropathy (PDN). Methods This was a double-blind, randomized, parallel-group, multi-center study in patients with symmetric distal sensory polyneuropathy due to type 1 or 2 diabetes and duration of neuropathic pain between 3 months and 5 years...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913849/dose-and-administration-period-play-a-key-role-in-the-effect-of-ceftriaxone-on-neuropathic-pain-in-cci-operated-rats
#7
K K Frederiksen, P Kristensen, P H Honoré, G Gegelashvili, O J Bjerrum
Introduction An unmet medical need for more effective therapies of neuropathic pain exits. Here modulation of the glutaminergic system represents an unexplored possibility. Down-regulation ofglutamate transporters potentiates pain transmission by delaying the removal of glutamate from the synapse. In the spinal cord, glutamate transporter 1 (GLT-1) is responsible for more than 90% of the glutamate uptake. Ceftriaxone, a β-lactam, is believed to induce the expression of GLT-1 through the transcriptional factor (NF-ºB) pathway, which results in induced promoter activity and thereby increased synthesis of GLT-1 protein...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913821/cognitive-modulation-of-experimental-pain-at-spinal-and-cortical-levels
#8
Mie Hviid Simonsen, Jakob Bredal Jensen, Ole Kæseler Andersen, Laura Petrini, Line Lindhardt Egsgaard, Carsten Dahl Mørch
Background/aims Descending modulation of the nociceptive system has proven to be pronounced in healthy humans. The descending modulation can be activated by rather distinct methods such as strong tonic painful stimulation or changes in the cognitive state. The extent of descending modulation on spinal pain processing remains unclear. Therefore, we assessed simultaneous cognitive modulation of spinal and cortical processing of experimental pain. Methods Painful (1.7 × pain threshold (PT)) and non-painful (0...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913808/sortilins-in-neuropathic-pain
#9
M Richner, O J Bjerrum, Y De Koninck, A Nykjaer, C B Vaegter
Background/aims The molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913750/neuropathic-pain-models-in-the-development-of-analgesic-drugs
#10
Per Hartvig Honoré, Anna Basnet, Laila Eljaja, Pernille Kristensen, Lene Munkholm Andersen, Signe Neustrup, Pia Møllgaard, Ole J Bjerrum
Introduction Animal disease models are predictive for signs seen in disease. They may rarely mimic all signs in a specific disease in humans with respect to etiology, cause or development. Several models have been developed for different pain states and the alteration of behavior has been interpreted as a response to external stimulus or expression of pain or discomfort. Considerable attention must be paid not to interpret other effects such as somnolence or motor impairment as a pain response and similarly not to misinterpret the response of analgesics...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913745/review-of-neuroimaging-studies-related-to-pain-modulation
#11
Lone Knudsen, Gitte Laue Petersen, Kathrine Næsted Nørskov, Lene Vase, Nanna Finnerup, Troels Staehelin Jensen, Peter Svensson
BACKGROUND AND PURPOSE: A noxious stimulus does not necessarily cause pain. Nociceptive signals arising from a noxious stimulus are subject to modulation via endogenous inhibitory and facilitatory mechanisms as they travel from the periphery to the dorsal horn or brainstem and on to higher brain sites. Research on the neural structures underlying endogenous pain modulation has largely been restricted to animal research due to the invasiveness of such studies (e.g., spinal cord transection, brain lesioning, brain site stimulation)...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913680/mechanisms-of-visceral-pain-in-health-and-functional-gastrointestinal-disorders
#12
REVIEW
Adam D Farmer, Qasim Aziz
Background and aims Chronic visceral pain is common both in patients with identifiable organic disease and also in those without any structural, biochemical or immunological abnormality such as in the functional gastrointestinal disorders (FGIDs). We aim to provide a contemporaneous summary of pathways involved in visceral nociception and how a variety of mechanisms may influence an individual's experience of visceral pain. Methods In this narrative review, we have brought together evidence through a detailed search of Medline in addition to using our experience and exposure to recent research developments from ourselves and other research groups...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29913639/proteomic-analysis-of-cerebrospinal-fluid-gives-insight-into-the-pain-relief-of-spinal-cord-stimulation
#13
Anne-Li Lind, Magnus Wetterhall, Marcus Sjödin, Torsten Gordh
Aims Neuropathic pain is caused by a lesion or disease of the somatosensory nervous system affecting approximately 2% of the population. Current pharmacological treatments are ineffective for more than 50% of the patients and often give much adverse effects. Spinal cord stimulation (SCS) is an alternative cost-effective treatment with high efficacy, prolonged pain relief, few side effects. We have compared the cerebrospinal fluid (CSF) proteomes from neuropathic pain patients during pain relief induced by SCS and during pain sensation without SCS, to gain further insights into the mechanisms behind the obtained analgesia...
December 29, 2017: Scandinavian Journal of Pain
https://www.readbyqxmd.com/read/29912587/gpcr-kinase-2-interacting-protein-1-protects-against-ischemia-reperfusion-injury-of-the-spinal-cord-by-modulating-ask1-jnk-p38-signaling
#14
Jian Chen, Qian Wang, Wei Zhou, Zheng Zhou, Peng-Yu Tang, Tao Xu, Wei Liu, Lin-Wei Li, Lin Cheng, Zhi-Min Zhou, Jin Fan, Guo-Yong Yin
GPCR kinase 2-interacting protein-1 (GIT1) is a scaffold protein that plays an important role in cell adaptation, proliferation, migration, and differentiation; however, the role of GIT1 in the regulation of neuronal death after spinal cord injury remains obscure. Here, we demonstrate that GIT1 deficiency remarkably increased neuronal apoptosis and enhanced JNK/p38 signaling, which resulted in stronger motor deficits by ischemia-reperfusion in vivo, consistent with the finding of oxygen-glucose deprivation/reoxygenation-induced neuronal injury in vitro...
June 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29912283/immune-evasive-gene-switch-enables-regulated-delivery-of-chondroitinase-after-spinal-cord-injury
#15
Emily R Burnside, Fred De Winter, Athanasios Didangelos, Nicholas D James, Elena-Cristina Andreica, Hugo Layard-Horsfall, Elizabeth M Muir, Joost Verhaagen, Elizabeth J Bradbury
Chondroitinase ABC is a promising preclinical therapy that promotes functional neuroplasticity after CNS injury by degrading extracellular matrix inhibitors. Efficient delivery of chondroitinase ABC to the injured mammalian spinal cord can be achieved by viral vector transgene delivery. This approach dramatically modulates injury pathology and restores sensorimotor functions. However, clinical development of this therapy is limited by a lack of ability to exert control over chondroitinase gene expression. Prior experimental gene regulation platforms are likely to be incompatible with the non-resolving adaptive immune response known to occur following spinal cord injury...
June 14, 2018: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29909452/correction-to-stem-cells-from-human-exfoliated-deciduous-teeth-modulate-early-astrocyte-response-after-spinal-cord-contusion
#16
Fabrício Nicola, Marília Rossato Marques, Felipe Odorcyk, Letícia Petenuzzo, Dirceu Aristimunha, Adriana Vizuete, Eduardo Farias Sanches, Daniela Pavulack Pereira, Natasha Maurmann, Carlos-Alberto Gonçalves, Patricia Pranke, Carlos Alexandre Netto
The authors hereby declare that the Figure 4 in page eight of the paper "Stem cells from human exfoliated deciduous teeth modulate early astrocyte response after spinal cord contusion" authored by Fabrício Nicola and colleagues (DOI: 10.1007/s12035-018-1127-4) was mistakenly included.
June 16, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29908959/low-back-pain-and-disc-degeneration-are-decreased-following-chronic-toll-like-receptor-4-inhibition-in-a-mouse-model
#17
Emerson Krock, Magali Millecamps, J Brooke Currie, Laura S Stone, Lisbet Haglund
OBJECTIVE: Intervertebral disc degeneration is a leading cause of chronic low back pain but current treatment is limited. Toll-like receptors (TLR) on disc cells are activated by endogenous extracellular matrix fragments and modulate degeneration in vitro. This study investigated whether inhibiting TLR4 slows disc degeneration and reduces behavioral signs of LBP in vivo. DESIGN: 7-9-month old wild-type and SPARC-null (a model of disc degeneration and LBP) male mice were treated with TAK-242 (TLR4 inhibitor) once, and following a 10-day washout, mice were treated 3 times/week for 8 weeks...
June 14, 2018: Osteoarthritis and Cartilage
https://www.readbyqxmd.com/read/29907859/the-microrna-10a-id3-runx2-axis-modulates-the-development-of-ossification-of-posterior-longitudinal-ligament
#18
Chen Xu, Hao Zhang, Wei Gu, Huiqiao Wu, Yuanyuan Chen, Wenchao Zhou, Baifeng Sun, Xiaolong Shen, Zicheng Zhang, Yue Wang, Yang Liu, Wen Yuan
Ossification of the posterior longitudinal ligament (OPLL) presents as pathological heterotopic ossification of the spinal ligaments. However, its underlying molecular mechanism is still unclear. Our previous findings suggested that altered microRNA regulatory network are critical for the development of OPLL. Here, we set out to unveiling the detailed mechanism of those altered OPLL-specific microRNAs. We screened a set of differentially expressed OPLL-specific microRNAs from the previous sequencing data and showed that microRNA-10a actively modulates the ossification of posterior ligament cells in vitro...
June 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29905656/pain-processing-in-the-human-brainstem-and-spinal-cord-before-during-and-after-the-application-of-noxious-heat-stimuli
#19
P W Stroman, G Ioachim, J M Powers, R Staud, C Pukall
Descending regulation of spinal cord responses to nociceptive signaling has a strong influence on pain perception. Prior studies using functional magnetic resonance imaging (fMRI) have indicated that in addition to reactive responses to nociceptive signals there is a continuous component to regulation, and that it may vary with differences in pain sensitivity. We hypothesize that this continuous regulation component occurs routinely in fMRI studies prior to noxious stimulation, as well as during, and following stimulation...
June 12, 2018: Pain
https://www.readbyqxmd.com/read/29904281/vrtn-is-required-for-the-development-of-thoracic-vertebrae-in-mammals
#20
Yanyu Duan, Hui Zhang, Zhen Zhang, Jun Gao, Jie Yang, Zhongping Wu, Yin Fan, Yuyun Xing, Lin Li, Shijun Xiao, Yong Hou, Jun Ren, Lusheng Huang
Vertnin ( VRTN ) variants are associated with thoracic vertebral number (TVN) in pigs. However, the biological function of VRTN remains poorly understood. Here we first conducted a range of experiments to demonstrate that VRTN is a responsible gene for TVN and two causative variants in the regulatory region of VRTN additively regulate TVN. Then, we show that VRTN is a novel DNA-binding transcription factor as it localizes exclusively in the nucleus, binds to DNA on a genome-wide scale and regulates the transcription of a set of genes that harbor VRTN binding motifs...
2018: International Journal of Biological Sciences
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