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https://www.readbyqxmd.com/read/29351125/central-inhibition-of-granulocyte-macrophage-colony-stimulating-factor-is-analgesic-in-experimental-neuropathic-pain
#1
Louise S C Nicol, Peter Thornton, Jon P Hatcher, Colin P Glover, Carl I Webster, Matthew Burrell, Kessia Hammett, Clare A Jones, Matthew A Sleeman, Andrew Billinton, Iain Chessell
With less than 50% of patients responding to the current standard of care and poor efficacy and selectivity of current treatments, neuropathic pain continues to be an area of considerable unmet medical need. Biological therapeutics such as monoclonal antibodies (mAbs) provide better intrinsic selectivity; however, delivery to the central nervous system (CNS) remains a challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is well described in inflammation-induced pain, and early-phase clinical trials evaluating its antagonism have exemplified its importance as a peripheral pain target...
January 16, 2018: Pain
https://www.readbyqxmd.com/read/29350777/the-pathology-of-lumbosacral-lipomas-macroscopic-and-microscopic-disparity-have-implications-for-embryogenesis-and-mode-of-clinical-deterioration
#2
Victoria Jones, Victoria Wykes, Nicki Cohen, Dominic Thompson, Thomas S Jacques
AIMS: Lumbosacral lipomas (LSL) are congenital disorders of the terminal spinal cord region that have the potential to cause significant spinal cord dysfunction in children. They are of unknown embryogenesis with variable clinical presentation and natural history. It is unclear whether the spinal cord dysfunction reflects a primary developmental dysplasia or whether it occurs secondarily to mechanical traction (spinal cord tethering) with growth. Whilst different anatomical subtypes are recognised and classified according to radiological criteria, these subtypes correlate poorly with clinical prognosis...
January 19, 2018: Histopathology
https://www.readbyqxmd.com/read/29344866/immuno-guided-laser-capture-microdissection-of-glial-cells-for-mrna-analysis
#3
Arnaud B Nicot, Justine Rambeau, Flora Guillot, Alexandra Garcia, David A Laplaud
Laser-capture microdissection (LCM) allows for retrieval of specific cell populations in situ. By combining immunofluorescent labeling with LCM, mRNAs can be probed by qRT-PCR for determining in situ gene expression during health and disease. This approach permits obtaining and analyzing histologically enriched cell populations in a tissue that can be hardly obtained from other methods such as white matter astrocytes from rodents or any individual cell population from archival human or rodent brain tissues...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29334787/analysis-of-endocannabinoid-receptors-and-enzymes-in-the-post-mortem-motor-cortex-and-spinal-cord-of-amyotrophic-lateral-sclerosis-patients
#4
Francisco Espejo-Porras, Javier Fernández-Ruiz, Eva de Lago
OBJECTIVE: We have investigated the endocannabinoid system in the motor cortex of motor neuron disease (MND) patients. METHODS: Post-mortem samples from MND patients and controls were used for immunostaining and/or Western blotting analysis of endocannabinoid elements. RESULTS: We did not find any evidence of neuronal losses in the motor cortex of MND patients, but elevations in glial markers Iba-1 and GFAP were evident. We found no changes in FAAH and MAGL enzymes and in the CB1 receptor, which correlated with the lack of cortical neuron death...
January 15, 2018: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/29330870/cell-therapy-for-spinal-cord-injury-with-olfactory-ensheathing-glia-cells-oecs
#5
REVIEW
Rosa M Gómez, Magdy Y Sánchez, Maria Portela-Lomba, Kemel Ghotme, George E Barreto, Javier Sierra, M Teresa Moreno-Flores
The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs)...
January 13, 2018: Glia
https://www.readbyqxmd.com/read/29327205/nociceptive-roles-of-trpm2-ion-channel-in-pathologic-pain
#6
REVIEW
Yongwoo Jang, Pyung Sun Cho, Young Duk Yang, Sun Wook Hwang
Pain is a protective mechanism that enables us to avoid potentially harmful environments. However, when pathologically persisted and aggravated under severely injured or inflamed conditions, pain often reduces the quality of life and thus is considered as a disease to eliminate. Inflammatory and/or neuropathic mechanisms may exaggerate interactions between damaged tissues and neural pathways for pain mediation. Similar mechanisms also promote the communication among cellular participants in synapses at spinal or higher levels, which may amplify nociceptive firing and subsequent signal transmission, deteriorating the pain sensation...
January 11, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29318865/-advances-in-acupuncture-mechanism-research-on-the-changes-of-synaptic-plasticity-pain-memory-for-chronic-pain
#7
Yi-Ling Yang, Jian-Peng Huang, Li Jiang, Jian-Hua Liu
Previous studies have shown that there are many common structures between the neural network of pain and memory, and the main structure in the pain network is also part of the memory network. Chronic pain is characterized by recurrent attacks and is associated with persistent ectopic impulse, which causes changes in synaptic structure and function based on nerve activity. These changes may induce long-term potentiation of synaptic transmission, and ultimately lead to changes in the central nervous system to produce "pain memory"...
December 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29315225/fm19g11-and-ependymal-progenitor-stem-cell-combinatory-treatment-enhances-neuronal-preservation-and-oligodendrogenesis-after-severe-spinal-cord-injury
#8
Ana Alastrue-Agudo, Francisco Javier Rodriguez-Jimenez, Eric López Mocholi, Francesca De Giorgio, Slaven Erceg, Victoria Moreno-Manzano
Spinal cord injury (SCI) suffers from a lack of effective therapeutic strategies. We have previously shown that individual therapeutic strategies, transplantation of ependymal stem/progenitor cells of the spinal cord after injury (epSPCi) or FM19G11 pharmacological treatment, induce moderate functional recovery after SCI. Here, the combination of treatments has been assayed for functional and histological analysis. Immediately after severe SCI, one million epSPCi were intramedullary injected, and the FM19G11 compound or dimethyl sulfoxide (DMSO) (as the vehicle control) was administrated via intrathecal catheterization...
January 9, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29298648/optogenetics-of-the-spinal-cord-use-of-channelrhodopsin-proteins-for-interrogation-of-spinal-cord-circuits
#9
Habibur Rahman, Youngpyo Nam, Jae-Hong Kim, Won-Ha Lee, Kyoungho Suk
Spinal cord circuits play a key role in receiving and transmitting somatosensory information from the body and the brain. They also contribute to the timing and coordination of complex patterns of movement. Under disease conditions, such as spinal cord injury and neuropathic pain, spinal cord circuits receive pain signals from peripheral nerves, and are involved in pain development via neurotransmitters and inflammatory mediators released from neurons and glial cells. Despite the importance of spinal cord circuits in sensory and motor functions, many questions remain regarding the relationship between activation of specific cells and behavioral responses...
December 29, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29285798/affected-astrocytes-in-the-spinal-cord-of-the-leukodystrophy-vanishing-white-matter
#10
Prisca S Leferink, Nicole Breeuwsma, Marianna Bugiani, Marjo S van der Knaap, Vivi M Heine
Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected...
December 29, 2017: Glia
https://www.readbyqxmd.com/read/29279310/proliferating-ng2-cell-dependent-angiogenesis-and-scar-formation-alter-axon-growth-and-functional-recovery-after-spinal-cord-injury-in-mice
#11
Z C Hesp, R Y Yoseph, R Suzuki, C Wilson, A Nishiyama, D M McTigue
Spinal cord injury (SCI) induces a centralized fibrotic scar surrounded by a reactive glial scar at the lesion site. The origin of these scars is thought to be perivascular cells entering lesions on ingrowing blood vessels and reactive astrocytes, respectively. However, two NG2-expressing cell populations (pericytes and glia) also may influence scar formation. In the periphery, new blood vessel growth requires proliferating NG2+ pericytes; if also true in the CNS, then the fibrotic scar would depend on dividing NG2+ pericytes...
December 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29276736/maternal-separation-stress-leads-to-resilience-against-neuropathic-pain-in-adulthood
#12
Julien Genty, Milène Tetsi Nomigni, Fernand Anton, Ulrike Hanesch
Early life stress (ELS) leads to a permanent reprogramming of biochemical stress response cascades that may also be relevant for the processing of chronic pain states such as neuropathy. Despite clinical evidence, little is known about ELS-related vulnerability for neuropathic pain and the possibly underlying etiology. In the framework of experimental studies aimed at investigating the respective relationships we used the established ELS model of maternal separation (MS). Rat dams and neonates were separated for 3 h/day from post-natal day 2-12...
February 2018: Neurobiology of Stress
https://www.readbyqxmd.com/read/29258553/prenatal-alcohol-exposure-is-a-risk-factor-for-adult-neuropathic-pain-via-aberrant-neuroimmune-function
#13
Joshua J Sanchez, Shahani Noor, Suzy Davies, Daniel Savage, Erin D Milligan
BACKGROUND: Clinical studies show that prenatal alcohol exposure (PAE) results in effects that persist into adulthood. Experimental animal models of moderate PAE demonstrate that young adults with PAE display potentiated sensitivity to light touch, clinically termed allodynia, following sciatic nerve chronic constriction injury (CCI) that coincides with heightened spinal glial, spinal macrophage, and peripheral immune responses. However, basal touch sensitivity and corresponding glial and leukocyte activation are unaltered...
December 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29239336/neural-progenitor-cells-but-not-astrocytes-respond-distally-to-thoracic-spinal-cord-injury-in-rat-models
#14
Tara Nguyen, Yilin Mao, Theresa Sutherland, Catherine Anne Gorrie
Traumatic spinal cord injury (SCI) is a detrimental condition that causes loss of sensory and motor function in an individual. Many complex secondary injury cascades occur after SCI and they offer great potential for therapeutic targeting. In this study, we investigated the response of endogenous neural progenitor cells, astrocytes, and microglia to a localized thoracic SCI throughout the neuroaxis. Twenty-five adult female Sprague-Dawley rats underwent mild-contusion thoracic SCI (n = 9), sham surgery (n = 8), or no surgery (n = 8)...
November 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/29238462/mechanisms-of-spinal-cord-injury-regeneration-in-zebrafish-a-systematic-review
#15
REVIEW
Zeynab Noorimotlagh, Mahla Babaie, Mahdi Safdarian, Tahereh Ghadiri, Vafa Rahimi-Movaghar
Objectives: To determine the molecular and cellular mechanisms of spinal cord regeneration in zebrafish. Materials and Methods: Medical databases of PubMed and Scopus were searched with following key words: Zebrafish; spinal cord injuries; regeneration; recovery of function. The map of mechanisms was performed using Xmind software. Results: Wnt/ß-catenin signaling, L1.1, L1.2, Major vault protein (MVP), contactin-2 and High mobility group box1 (HMGB1) had positive promoting effects on axonal re-growth while Ptena had an inhibitory effect...
December 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29236326/knockdown-of-ski-decreased-the-reactive-astrocytes-proliferation-in-vitro-induced-by-oxygen-glucose-deprivation-reoxygenation
#16
Xin Zhao, Kai-Sheng Zhou, Zhong-Hao Li, Wei Nan, Jing Wang, Ya-Yi Xia, Hai-Hong Zhang
Glia scar is a pathological marker in late phase of brain ischemia disease, which constitutes a major physical biochemical barrier to impede axonal regrowth. Astrocytes are known to be critically involved in the formation of glial scar. However, their response to ischemia and their role in neuroprotection after central nervous system (CNS) injury are not completely clear. Recently, we have demonstrated for the first time that Ski was up-regulated in reactive astrocytes after spinal cord injury in vivo and in vitro, which indicates Ski may be a new molecule that control astrocytes biologic properties after CNS injury...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29228949/a-mathematical-model-for-histamine-synthesis-release-and-control-in-varicosities
#17
Janet Best, H F Nijhout, Srimal Samaranayake, Parastoo Hashemi, Michael Reed
BACKGROUND: Histamine (HA), a small molecule that is synthesized from the amino acid histidine, plays an important role in the immune system where it is associated with allergies, inflammation, and T-cell regulation. In the brain, histamine is stored in mast cells and other non-neuronal cells and also acts as a neurotransmitter. The histamine neuron cell bodies are in the tuberomammillary (TM) nucleus of the hypothalamus and these neurons send projections throughout the central nervous system (CNS), in particular to the cerebral cortex, amygdala, basal ganglia, hippocampus, thalamus, retina, and spinal cord...
December 12, 2017: Theoretical Biology & Medical Modelling
https://www.readbyqxmd.com/read/29228020/transplantation-of-canine-olfactory-ensheathing-cells-producing-chondroitinase-abc-promotes-chondroitin-sulphate-proteoglycan-digestion-and-axonal-sprouting-following-spinal-cord-injury
#18
Darren Carwardine, Jonathan Prager, Jacob Neeves, Elizabeth M Muir, James Uney, Nicolas Granger, Liang-Fong Wong
Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury...
2017: PloS One
https://www.readbyqxmd.com/read/29226998/antisense-suppression-of-glial-fibrillary-acidic-protein-as-a-treatment-for-alexander-disease
#19
Tracy L Hagemann, Berit Powers, Curt Mazur, Aneeza Kim, Steven Wheeler, Gene Hung, Eric Swayze, Albee Messing
OBJECTIVE: Alexander disease is a fatal leukodystrophy caused by autosomal dominant gain-of-function mutations in the gene for glial fibrillary acidic protein (GFAP), an intermediate filament protein primarily expressed in astrocytes of the central nervous system. A key feature of pathogenesis is over-expression and accumulation of GFAP, with formation of characteristic cytoplasmic aggregates known as Rosenthal fibers. Here we investigate whether suppressing GFAP with antisense oligonucleotides could provide a therapeutic strategy for treating Alexander disease...
December 11, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/29225571/heterogenic-distribution-of-aromatic-l-amino-acid-decarboxylase-neurons-in-the-rat-spinal-cord
#20
Li-Qun Ren, Meng Chen, Hans Hultborn, Sen Guo, Yifan Zhang, Mengliang Zhang
Aromatic L-amino acid decarboxylase (AADC) is an essential enzyme in the synthesis of serotonin, dopamine, and certain trace amines and is present in a variety of organs including the brain and spinal cord. It is previously reported that in mammalian spinal cord AADC cells (called D-cells) were largely confined to a region around the central canal and that they do not produce monoamines. To date, there has not been a detailed description of their distribution and morphology in mammals. In the present study this issue is systematically investigated using immunohistochemistry...
2017: Frontiers in Integrative Neuroscience
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