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https://www.readbyqxmd.com/read/28544775/potentiation-of-spinal-glutamatergic-response-in-the-neuron-glia-interactions-underlies-the-intrathecal-il-1%C3%AE-induced-thermal-hyperalgesia-in-rats
#1
Chun-Sung Sung, Zhi-Hong Wen, Chien-Wei Feng, Chun-Hong Chen, Shi-Ying Huang, Nan-Fu Chen, Wu-Fu Chen, Chih-Shung Wong
AIMS: We previously demonstrated that intrathecal IL-1β upregulated phosphorylation of p38 mitogen-activated protein kinase (P-p38 MAPK) and inducible nitric oxide synthase (iNOS) in microglia and astrocytes in spinal cord, increased nitric oxide (NO) release into cerebrospinal fluid, and induced thermal hyperalgesia in rats. This study investigated the role of spinal glutamatergic response in intrathecal IL-1β-induced nociception in rats. METHODS: The pretreatment effects of MK-801 (5 μg), minocycline (20 μg), and SB203580 (5 μg) on intrathecal IL-1β (100 ng) in rats were measured by behavior, Western blotting, CSF analysis, and immunofluorescence studies...
May 19, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28539349/sleep-loss-promotes-astrocytic-phagocytosis-and-microglial-activation-in-mouse-cerebral-cortex
#2
Michele Bellesi, Luisa de Vivo, Mattia Chini, Francesca Gilli, Giulio Tononi, Chiara Cirelli
We previously found that Mertk and its ligand Gas6, astrocytic genes involved in phagocytosis, are upregulated after acute sleep deprivation. These results suggested that astrocytes may engage in phagocytic activity during extended wake, but direct evidence was lacking. Studies in humans and rodents also found that sleep loss increases peripheral markers of inflammation, but whether these changes are associated with neuroinflammation and/or activation of microglia, the brain's resident innate immune cells, was unknown...
May 24, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28534275/sex-bias-in-pathogenesis-of-autoimmune-neuroinflammation-relevance-for-dimethyl-fumarate-immunomodulatory-anti-oxidant-action
#3
Zorica Stojić-Vukanić, Jelena Kotur-Stevuljević, Mirjana Nacka-Aleksić, Duško Kosec, Ivana Vujnović, Ivan Pilipović, Mirjana Dimitrijević, Gordana Leposavić
In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset...
May 22, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28526328/acrylamide-induced-neurotoxicity-in-primary-astrocytes-and-microglia-roles-of-the-nrf2-are-and-nf-%C3%AE%C2%BAb-pathways
#4
Mengyao Zhao, Fu Sheng Lewis Wang, Xiaosong Hu, Fang Chen, Hing Man Chan
Acrylamide (AA) is a common food contaminant formed during food heat processing that has neurotoxic effects. We hypothesize that AA induces oxidative stress in astrocytes and microglia, leading to neurotoxicity. Oxidative status, translocation of Nrf2 and NF-κB, and related down-stream targets were measured in primary astrocytes and microglia obtained from BALB/c mice. The results showed that AA increased reactive oxygen species (ROS) formation and reduced glutathione levels, causing successive events associated with oxidative stress, including 4-hydroxynonenal and 8-hydroxy-2-deoxyguanosine adduct formation, in both cell types...
May 16, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28521131/diverse-requirements-for-microglial-survival-specification-and-function-revealed-by-defined-medium-cultures
#5
Christopher J Bohlen, F Chris Bennett, Andrew F Tucker, Hannah Y Collins, Sara B Mulinyawe, Ben A Barres
Microglia, the resident macrophages of the CNS, engage in various CNS-specific functions that are critical for development and health. To better study microglia and the properties that distinguish them from other tissue macrophage populations, we have optimized serum-free culture conditions to permit robust survival of highly ramified adult microglia under defined-medium conditions. We find that astrocyte-derived factors prevent microglial death ex vivo and that this activity results from three primary components, CSF-1/IL-34, TGF-β2, and cholesterol...
May 17, 2017: Neuron
https://www.readbyqxmd.com/read/28495139/high-yield-primary-microglial-cultures-using-granulocyte-macrophage-colony-stimulating-factor-from-embryonic-murine-cerebral-cortical-tissue
#6
Adam C Yu, Sarah E Neil, Jacqueline A Quandt
BACKGROUND: Microglia play vital roles in neurotrophic support and modulating immune or inflammatory responses to pathogens or damage/stressors during disease. This study describes the ability to establish large numbers of microglia from embryonic tissues with the addition of granulocyte-macrophage stimulating factor (GM-CSF) and characterizes their similarities to adult microglia examined ex vivo as well as their responses to inflammatory mediators. METHOD: Microglia were seeded from a primary embryonic mixed cortical suspension with the addition of GM-CSF...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28480882/dysfunction-of-microglial-stat3-alleviates-depressive-behavior-via-neuron-microglia-interactions
#7
Sun-Ho Kwon, Jeong-Kyu Han, Moonseok Choi, Yong-Jin Kwon, Sung Joon Kim, Eun Hee Yi, Jae-Cheon Shin, Ik-Hyun Cho, Byung-Hak Kim, Sang Jeong Kim, Sang-Kyu Ye
Neuron-microglia interactions play a crucial role in maintaining the neuroimmune system. The balance of neuroimmune system has emerged as an important process in the pathophysiology of depression. However, how neuron-microglia interactions contribute to major depressive disorders has been poorly understood. Herein, we demonstrated that microglia-derived synaptic changes induced antidepressive-like behavior by using microglia-specific signal transducer and activator of transcription 3 (STAT3) knockout (STAT3(fl/fl);LysM-Cre(+/-)) mice...
May 8, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28458957/dramatic-effect-of-oral-csf-1r-kinase-inhibitor-on-retinal-microglia-revealed-by-in-vivo-scanning-laser-ophthalmoscopy
#8
Andreas Ebneter, Despina Kokona, Joël Jovanovic, Martin S Zinkernagel
This report provides sound evidence that the small molecule pharmaceutical PLX5622, a highly selective CSF-1R kinase inhibitor, crosses the blood-retina barrier and suppresses microglia activity. Members of this class of drug are in advanced clinical development stages and may represent a novel approach to modulate ocular inflammatory processes.
April 2017: Translational Vision Science & Technology
https://www.readbyqxmd.com/read/28441917/identification-of-il-17a-derived-neural-cell-type-and-dynamic-changes-of-il-17a-in-serum-csf-of-mice-with-ischemic-stroke
#9
Shujuan Li, Qingqing Dai, Jinling Yu, Ting Liu, Shuiqiao Liu, Longhui Ma, Ying Zhang, Song Han, Junfa Li
BACKGROUND: Interleukin (IL)-17A was reported to be involved in the development of post-ischemic stroke inflammatory response and functional recovery. However, the IL-17A dynamic changes in serum/cerebrospinal fluid (CSF) and its role in neuronal injury following ischemic stroke are unclear. METHODS: In vivo ischemic stroke was induced by 1 h of middle cerebral artery occlusion (MCAO) and 6 h-7 d reperfusion (R) in mice, while in vitro stroke was induced by 1 h oxygen-glucose deprivation (OGD)/24 h reoxygenation (R) in cultured cortical neurons...
June 2017: Neurological Research
https://www.readbyqxmd.com/read/28434164/microglia-loss-contributes-to-the-development-of-major-depression-induced-by-different-types-of-chronic-stresses
#10
Lijuan Tong, Yu Gong, Peng Wang, Wenfeng Hu, Jili Wang, Zhuo Chen, Wei Zhang, Chao Huang
Recently, the loss and dystrophy of hippocampal microglia induced by chronic unpredictable stress (CUS) has been reported to mediate the development of major depression in mice whose microglial cells were labeled with enhanced green fluorescent protein-conjuncted-CX3C receptor type 1. However, whether this happens in endogenous microglia with no genetic intervention remains unclear. Here, we addressed this issue in mice treated with different types of chronic stresses, including the CUS, chronic restraint stress (CRS) and chronic social defeat stress (CSDS)...
April 22, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28416596/microrna-profiling-reveals-marker-of-motor-neuron-disease-in-als-models
#11
Mariah L Hoye, Erica D Koval, Amy J Wegener, Theodore S Hyman, Chengran Yang, David R O'Brien, Rebecca L Miller, Tracy Cole, Kathleen M Schoch, Tao Shen, Tomonori Kunikata, Jean-Philippe Richard, David H Gutmann, Nicholas J Maragakis, Holly B Kordasiewicz, Joseph D Dougherty, Timothy M Miller
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in the brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed to characterize the distinct expression profile of that cell type in order to elucidate underlying disease mechanisms and identify novel targets that inform on MN health during ALS disease timecourse. microRNAs (miRNAs) are short, non-coding RNAs that can shape the expression profile of a cell and, consequently, often exhibit cell type enriched expression...
April 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28340598/myelin-specific-multiple-sclerosis-antibodies-cause-complement-dependent-oligodendrocyte-loss-and-demyelination
#12
Yiting Liu, Katherine S Given, Danielle E Harlow, Adeline M Matschulat, Wendy B Macklin, Jeffrey L Bennett, Gregory P Owens
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF. Among these were a subset of myelin-specific MS rAbs. We examined their immunoreactivity to mouse organotypic cerebellar slices by live binding and evaluated tissue injury in the presence and absence of human complement...
March 24, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28274846/acute-granulocyte-macrophage-colony-stimulating-factor-treatment-modulates-neuroinflammatory-processes-and-promotes-tactile-recovery-after-spinal-cord-injury
#13
Sandie Thomaty, Laurent Pezard, Christian Xerri, Jean-Michel Brezun
Neuroinflammation is known to play a key role in the prognosis of functional recovery after spinal cord injury (SCI). The involvement of microglial and mast cells in early and late stages of inflammation has been receiving increasing attention. This study was aimed at determining the influence of a pro-inflammatory cytokine, the granulocyte macrophage-colony stimulating factor (GM-CSF), on microglia and mast cell activation, glial scar formation and functional recovery following SCI. Rats were randomly injected with saline or GM-CSF one hour after a C4-C5 medio-lateral hemisection...
May 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28236968/regulation-of-embryonic-and-postnatal-development-by-the-csf-1-receptor
#14
REVIEW
Violeta Chitu, E Richard Stanley
Macrophages are found in all tissues and regulate tissue morphogenesis during development through trophic and scavenger functions. The colony stimulating factor-1 (CSF-1) receptor (CSF-1R) is the major regulator of tissue macrophage development and maintenance. In combination with receptor activator of nuclear factor κB (RANK), the CSF-1R also regulates the differentiation of the bone-resorbing osteoclast and controls bone remodeling during embryonic and early postnatal development. CSF-1R-regulated macrophages play trophic and remodeling roles in development...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28183245/ykl-40-as-a-potential-biomarker-and-a-possible-target-in-therapeutic-strategies-of-alzheimer-s-disease
#15
Paweł Muszyński, Magdalena Groblewska, Agnieszka Kulczyńska-Przybik, Alina Kułakowska, Barbara Mroczko
BACKGROUND: Growing body of evidence suggests that pathogenesis of Alzheimer's disease (AD), a progressing neurodegenerative condition, is not limited to the neuronal compartment, but also involves various immunological mechanisms. Insoluble Aβ aggregates in the brain can induce the activation of microglia, resulting in synthesis of proinflammatory mediators, which further can stimulate astrocytic expression of YKL-40. Therefore, the aim of the current review is to present up-to-date data about the role of YKL-40 as a biomarker of AD as well as the possibility of therapeutic strategies targeting neuroinflammation...
February 8, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28177105/the-circumventricular-organs
#16
REVIEW
Charanjit Kaur, Eng-Ang Ling
The circumventricular organs (CVOs) are midline structures located around the third and fourth ventricles that are characterized by a lack of blood-brain barrier. The pineal gland, median eminence, neurohypophysis and the subcommisural organ are classified as secretory, whereas the subfornical organ, area postrema and the organum vasculosum of the lamina terminalis as the sensory CVOs. Glial cells consisting of astrocytes and microglia/macrophages are present in all these organs. The pineal gland, neurohypophysis and the median eminence lack the presence of neurons that are present in the rest of the circumventricular organs...
February 8, 2017: Histology and Histopathology
https://www.readbyqxmd.com/read/28159556/activated-microglia-trigger-inflammasome-activation-and-lysosomal-destabilization-in-human-rpe-cells
#17
Christopher Nebel, Alexander Aslanidis, Khalid Rashid, Thomas Langmann
Activation of the innate immune system plays a major role in retinal degenerative diseases including age-related macular degeneration (AMD). In this study, we investigated whether reactive microglia trigger and sustain NLRP3 inflammasome activation in human retinal pigment epithelium (ARPE-19) cells. Specifically, we analyzed the potential of cell culture supernatants from lipopolysaccharide (LPS)-stimulated human microglia in combination with the lysosomal destabilization agent Leu-Leu-O-Me (LLOMe) to activate the inflammasome in ARPE-19 cells...
March 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28153013/effects-of-dexamethasone-and-meloxicam-on-borrelia-burgdorferi-induced-inflammation-in-glial-and-neuronal-cells-of-the-central-nervous-system
#18
Geeta Ramesh, Alejandra N Martinez, Dale S Martin, Mario T Philipp
BACKGROUND: Lyme neuroborreliosis (LNB), caused by the spirochete Borrelia burgdorferi (Bb), affects both the central and peripheral nervous systems. Previously, we reported that in a model of acute LNB in rhesus monkeys, treatment with the anti-inflammatory drug dexamethasone significantly reduced both pleocytosis and levels of cerebrospinal fluid (CSF) immune mediators that were induced by Bb. Dexamethasone also inhibited the formation of inflammatory, neurodegenerative, and demyelinating lesions in the brain and spinal cord of these animals...
February 2, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28137632/generation-6-hydroxyl-pamam-dendrimers-improve-cns-penetration-from-intravenous-administration-in-a-large-animal-brain-injury-model
#19
Fan Zhang, J Trent Magruder, Yi-An Lin, Todd C Crawford, Joshua C Grimm, Christopher M Sciortino, Mary Ann Wilson, Mary E Blue, Sujatha Kannan, Michael V Johnston, William A Baumgartner, Rangaramanujam M Kannan
Hypothermic circulatory arrest (HCA) provides neuroprotection during cardiac surgery but entails an ischemic period that can lead to excitotoxicity, neuroinflammation, and subsequent neurologic injury. Hydroxyl polyamidoamine (PAMAM) dendrimers target activated microglia and damaged neurons in the injured brain, and deliver therapeutics in small and large animal models. We investigated the effect of dendrimer size on brain uptake and explored the pharmacokinetics in a clinically-relevant canine model of HCA-induced brain injury...
March 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28128358/galectin-3-released-in-response-to-traumatic-brain-injury-acts-as-an-alarmin-orchestrating-brain-immune-response-and-promoting-neurodegeneration
#20
Ping Kei Yip, Alejandro Carrillo-Jimenez, Paul King, Anna Vilalta, Koji Nomura, Chi Cheng Chau, Alexander Michael Scott Egerton, Zhuo-Hao Liu, Ashray Jayaram Shetty, Jordi L Tremoleda, Meirion Davies, Tomas Deierborg, John V Priestley, Guy Charles Brown, Adina Teodora Michael-Titus, Jose Luis Venero, Miguel Angel Burguillos
Traumatic brain injury (TBI) is currently a major cause of morbidity and poor quality of life in Western society, with an estimate of 2.5 million people affected per year in Europe, indicating the need for advances in TBI treatment. Within the first 24 h after TBI, several inflammatory response factors become upregulated, including the lectin galectin-3. In this study, using a controlled cortical impact (CCI) model of head injury, we show a large increase in the expression of galectin-3 in microglia and also an increase in the released form of galectin-3 in the cerebrospinal fluid (CSF) 24 h after head injury...
January 27, 2017: Scientific Reports
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