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https://www.readbyqxmd.com/read/29238736/combination-of-fluorescent-in-situ-hybridization-fish-and-immunofluorescence-imaging-for-detection-of-cytokine-expression-in-microglia-macrophage-cells
#1
Maria Fe Lanfranco, David J Loane, Italo Mocchetti, Mark P Burns, Sonia Villapol
Microglia and macrophage cells are the primary producers of cytokines in response to neuroinflammatory processes. But these cytokines are also produced by other glial cells, endothelial cells, and neurons. It is essential to identify the cells that produce these cytokines to target their different levels of activation. We used dual RNAscope® fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) techniques to visualize the mRNA expression pattern of pro- and anti-inflammatory cytokines in microglia/macrophages cells...
November 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29201010/microglia-and-brain-plasticity-in-acute-psychosis-and-schizophrenia-illness-course-a-meta-review
#2
REVIEW
Livia J De Picker, Manuel Morrens, Steven A Chance, Delphine Boche
Objective: Schizophrenia poses a tremendous health, social, and economic burden upon patients and society, indicating current treatment options remain inadequate. Recent findings from several lines of evidence have pointed to the importance of immune system involvement in not only premorbid neurodevelopmental but also subsequent symptom generation and aging processes of brain change in schizophrenia. In this meta-review, we use the summarized evidence from recent quantitative systematic reviews (SRs) and meta-analyses of several subspecialties to critically evaluate the hypothesis that immune-related processes shape the symptomatic presentation and illness course of schizophrenia, both directly and indirectly through altered neuroplasticity...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29064155/assessing-inflammation-in-acute-intracerebral-hemorrhage-with-pk11195-pet-and-dynamic-contrast-enhanced-mri
#3
Kamran A Abid, Oluwaseun A Sobowale, Laura M Parkes, Josephine Naish, Geoff J M Parker, Daniel du Plessis, David Brough, Jack Barrington, Stuart M Allan, Rainer Hinz, Adrian R Parry-Jones
BACKGROUND AND PURPOSE: Studies in animal models suggest that inflammation is a major contributor to secondary injury after intracerebral hemorrhage (ICH). Direct, noninvasive monitoring of inflammation in the human brain after ICH will facilitate early-phase development of anti-inflammatory treatments. We sought to investigate the feasibility of multimodality brain imaging in subacute ICH. METHODS: Acute ICH patients were recruited to undergo multiparametric MRI (including dynamic contrast-enhanced measurement of blood-brain barrier transfer constant (K(trans) ) and PET with [(11) C]-(R)-PK11195)...
October 24, 2017: Journal of Neuroimaging: Official Journal of the American Society of Neuroimaging
https://www.readbyqxmd.com/read/29038483/quantitative-microglia-analyses-reveal-diverse-morphologic-responses-in-the-rat-cortex-after-diffuse-brain-injury
#4
Helena Morrison, Kimberly Young, Mahir Qureshi, Rachel K Rowe, Jonathan Lifshitz
Determining regions of altered brain physiology after diffuse brain injury is challenging. Microglia, brain immune cells with ramified and dynamically moving processes, constantly surveil the parenchyma for dysfunction which, when present, results in a changed morphology. Our purpose was to define the spatiotemporal changes in microglia morphology over 28 days following rat midline fluid percussion injury (mFPI) as a first step in exploiting microglia morphology to reflect altered brain physiology. Microglia morphology was quantified from histological sections using Image J skeleton and fractal analysis procedures at three time points and in three regions post-mFPI: impact site, primary somatosensory cortex barrel field (S1BF), and a remote region...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28874660/integrative-genomics-of-microglia-implicates-dlg4-psd95-in-the-white-matter-development-of-preterm-infants
#5
Michelle L Krishnan, Juliette Van Steenwinckel, Anne-Laure Schang, Jun Yan, Johanna Arnadottir, Tifenn Le Charpentier, Zsolt Csaba, Pascal Dournaud, Sara Cipriani, Constance Auvynet, Luigi Titomanlio, Julien Pansiot, Gareth Ball, James P Boardman, Andrew J Walley, Alka Saxena, Ghazala Mirza, Bobbi Fleiss, A David Edwards, Enrico Petretto, Pierre Gressens
Preterm birth places infants in an adverse environment that leads to abnormal brain development and cerebral injury through a poorly understood mechanism known to involve neuroinflammation. In this study, we integrate human and mouse molecular and neuroimaging data to investigate the role of microglia in preterm white matter damage. Using a mouse model where encephalopathy of prematurity is induced by systemic interleukin-1β administration, we undertake gene network analysis of the microglial transcriptomic response to injury, extend this by analysis of protein-protein interactions, transcription factors and human brain gene expression, and translate findings to living infants using imaging genomics...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28846081/microglia-turnover-with-aging-and-in-an-alzheimer-s-model-via-long-term-in-vivo-single-cell-imaging
#6
Petra Füger, Jasmin K Hefendehl, Karthik Veeraraghavalu, Ann-Christin Wendeln, Christine Schlosser, Ulrike Obermüller, Bettina M Wegenast-Braun, Jonas J Neher, Peter Martus, Shinichi Kohsaka, Martin Thunemann, Robert Feil, Sangram S Sisodia, Angelos Skodras, Mathias Jucker
To clarify the role of microglia in brain homeostasis and disease, an understanding of their maintenance, proliferation and turnover is essential. The lifespan of brain microglia, however, remains uncertain, and reflects confounding factors in earlier assessments that were largely indirect. We genetically labeled single resident microglia in living mice and then used multiphoton microscopy to monitor these cells over time. Under homeostatic conditions, we found that neocortical resident microglia were long-lived, with a median lifetime of well over 15 months; thus, approximately half of these cells survive the entire mouse lifespan...
October 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28836304/impaired-microglia-process-dynamics-post-stroke-are-specific-to-sites-of-secondary-neurodegeneration
#7
Murielle G Kluge, Laura Kracht, Mahmoud Abdolhoseini, Lin Kooi Ong, Sarah J Johnson, Michael Nilsson, Frederick R Walker
Stroke induces tissue death both at the site of infarction and at secondary sites connected to the primary infarction. This latter process has been referred to as secondary neurodegeneration (SND). Using predominantly fixed tissue analyses, microglia have been implicated in regulating the initial response at both damage sites post-stroke. In this study, we used acute slice based multiphoton imaging, to investigate microglia dynamic process movement in mice 14 days after a photothrombotic stroke. We evaluated the baseline motility and process responses to locally induced laser damage in both the peri-infarct (PI) territory and the ipsilateral thalamus, a major site of post-stroke SND...
August 24, 2017: Glia
https://www.readbyqxmd.com/read/28757366/ibuprofen-does-not-reverse-ventilatory-acclimatization-to-chronic-hypoxia
#8
D J De La Zerda, J A Stokes, J Do, A Go, Z Fu, F L Powell
Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic ventilatory response that is blocked by non-steroidal anti-inflammatory drugs administered during sustained hypoxia. We tested the hypothesis that inflammatory signals are necessary to sustain ventilatory acclimatization to hypoxia once it is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH, PiO2=70Torr) for 11-12days and treated with ibuprofen or saline for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood gas responses to O2 and CO2 were not affected by ibuprofen after acclimatization had been established...
July 27, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28713239/increased-white-matter-inflammation-in-aging-and-alzheimer-s-disease-brain
#9
Divya Raj, Zhuoran Yin, Marjolein Breur, Janine Doorduin, Inge R Holtman, Marta Olah, Ietje J Mantingh-Otter, Debby Van Dam, Peter P De Deyn, Wilfred den Dunnen, Bart J L Eggen, Sandra Amor, Erik Boddeke
Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28606377/comparative-morphology-and-phagocytic-capacity-of-primary-human-adult-microglia-with-time-lapse-imaging
#10
Natalie Levtova, Luke M Healy, Catalina Marysol Carvajal Gonczi, Brandon Stopnicki, Manon Blain, Timothy E Kennedy, Craig S Moore, Jack P Antel, Peter J Darlington
Microglia provide immune surveillance within the brain and spinal cord. Various microglial morphologies include ramified, amoeboid, and pseudopodic. The link between form and function is not clear, especially for human adult microglia which are limited in availability for study. Here, we examined primary human microglia isolated from normal-appearing white matter. Pseudopodic and amoeboid microglia were effective phagocytes, taking up E. coli bioparticles using ruffled cell membrane sheets and retrograde transport...
September 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28529627/-18-f-ge-180-pet-detects-reduced-microglia-activation-after-lm11a-31-therapy-in-a-mouse-model-of-alzheimer-s-disease
#11
Michelle L James, Nadia P Belichenko, Adam J Shuhendler, Aileen Hoehne, Lauren E Andrews, Christina Condon, Thuy-Vi V Nguyen, Vladimer Reiser, Paul Jones, William Trigg, Jianghong Rao, Sanjiv S Gambhir, Frank M Longo
Microglial activation is a key pathological feature of Alzheimer's disease (AD). PET imaging of translocator protein 18 kDa (TSPO) is a strategy to detect microglial activation in vivo. Here we assessed flutriciclamide ([(18)F]GE-180), a new second-generation TSPO-PET radiotracer, for its ability to monitor response to LM11A-31, a novel AD therapeutic in clinical trials. AD mice displaying pathology were treated orally with LM11A-31 for 3 months. Subsequent [(18)F]GE-180-PET imaging revealed significantly lower signal in cortex and hippocampus of LM11A-31-treated AD mice compared to those treated with vehicle, corresponding with decreased levels of TSPO immunostaining and microglial Iba1 immunostaining...
2017: Theranostics
https://www.readbyqxmd.com/read/28498852/ultra-high-field-7tesla-magnetic-resonance-spectroscopy-in-amyotrophic-lateral-sclerosis
#12
Nazem Atassi, Maosheng Xu, Christina Triantafyllou, Boris Keil, Robert Lawson, Paul Cernasov, Elena Ratti, Christopher J Long, Sabrina Paganoni, Alyssa Murphy, Nouha Salibi, Ravi Seethamraju, Bruce Rosen, Eva-Maria Ratai
The main objective of this study was to utilize high field (7T) in vivo proton magnetic resonance imaging to increase the ability to detect metabolite changes in people with ALS, specifically, to quantify levels of glutamine and glutamine separately. The second objective of this study was to correlate metabolic markers with clinical outcomes of disease progression. 13 ALS participants and 12 age-matched healthy controls (HC) underwent 7 Tesla MRI and MRS. Single voxel MR spectra were acquired from the left precentral gyrus using a very short echo time (TE = 5 ms) STEAM sequence...
2017: PloS One
https://www.readbyqxmd.com/read/28381303/retention-of-normal-glia-function-by-an-isoform-selective-protein-kinase-inhibitor-drug-candidate-that-modulates-cytokine-production-and-cognitive-outcomes
#13
Zhengqiu Zhou, Adam D Bachstetter, Claudia B Späni, Saktimayee M Roy, D Martin Watterson, Linda J Van Eldik
BACKGROUND: Brain p38α mitogen-activated protein kinase (MAPK), a potential therapeutic target for cognitive dysfunction based on the neuroinflammation-synaptic dysfunction cycle of pathophysiology progression, offers an innovative pharmacological strategy via inhibiting the same activated target in both glia and neurons, thereby enhancing the possibility for efficacy. The highly selective, brain-penetrant p38αMAPK inhibitor MW150 attenuates cognitive dysfunction in two distinct Alzheimer's disease (AD)-relevant models and avoids the problems encountered with previous mixed-kinase inhibitor drug candidates...
April 5, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28361437/effect-of-preventive-and-curative-fingolimod-treatment-regimens-on-microglia-activation-and-disease-progression-in-a-rat-model-of-multiple-sclerosis
#14
David Vállez García, Janine Doorduin, Daniele de Paula Faria, Rudi A J O Dierckx, Erik F J de Vries
Fingolimod was the first oral drug approved for multiple sclerosis treatment. Its principal mechanism of action is blocking of lymphocyte trafficking. In addition, recent studies have shown its capability to diminish microglia activation. The effect of preventive and curative fingolimod treatment on the time-course of neuroinflammation was investigated in the experimental autoimmune encephalomyelitis rat model for multiple sclerosis. Neuroinflammatory progression was followed in Dark Agouti female rats after immunization...
September 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28358926/genetically-engineered-rat-gliomas-pdgf-driven-tumor-initiation-and-progression-in-tv-a-transgenic-rats-recreate-key-features-of-human-brain-cancer
#15
Nina P Connolly, Jesse A Stokum, Craig S Schneider, Tatsuya Ozawa, Su Xu, Rebeca Galisteo, Rudolph J Castellani, Anthony J Kim, J Marc Simard, Jeffrey A Winkles, Eric C Holland, Graeme F Woodworth
Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS) virus / tumor virus receptor-A (tv-a) transgenic system of post-natal cell type-specific gene transfer...
2017: PloS One
https://www.readbyqxmd.com/read/28242869/in-vivo-imaging-of-translocator-protein-a-marker-of-activated-microglia-in-alcohol-dependence
#16
A T Hillmer, C M Sandiego, J Hannestad, G A Angarita, A Kumar, E M McGovern, Y Huang, K C O'Connor, R E Carson, S S O'Malley, K P Cosgrove
Neuroinflammation may be a critical component of the neurobiology of alcohol use disorders, yet the exact nature of this relationship is not well understood. This work compared the brain and peripheral immune profile of alcohol-dependent subjects and controls. Brain levels of 18-kDa translocator protein (TSPO), a marker of microglial activation and neuroinflammation, were measured with [(11)C]PBR28 positron emission tomography imaging in 15 healthy controls and 15 alcohol-dependent subjects. Alcohol-dependent subjects were imaged 1-4 days (n=14) or 24 days (n=1) after their last drink...
February 28, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28122877/an-early-and-late-peak-in-microglial-activation-in-alzheimer-s-disease-trajectory
#17
Zhen Fan, David J Brooks, Aren Okello, Paul Edison
Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease...
March 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28111081/phosphatidylserine-exposure-controls-viral-innate-immune-responses-by-microglia
#18
Yusuf Tufail, Daniela Cook, Lawrence Fourgeaud, Colin J Powers, Katharina Merten, Charles L Clark, Elizabeth Hoffman, Alexander Ngo, Kohei J Sekiguchi, Clodagh C O'Shea, Greg Lemke, Axel Nimmerjahn
Microglia are the intrinsic immune sentinels of the central nervous system. Their activation restricts tissue injury and pathogen spread, but in some settings, including viral infection, this response can contribute to cell death and disease. Identifying mechanisms that control microglial responses is therefore an important objective. Using replication-incompetent adenovirus 5 (Ad5)-based vectors as a model, we investigated the mechanisms through which microglia recognize and respond to viral uptake. Transgenic, immunohistochemical, molecular-genetic, and fluorescence imaging approaches revealed that phosphatidylserine (PtdSer) exposure on the outer leaflet of transduced cells triggers their engulfment by microglia through TAM receptor-dependent mechanisms...
February 8, 2017: Neuron
https://www.readbyqxmd.com/read/28101527/regulation-of-physical-microglia-neuron-interactions-by-fractalkine-signaling-after-status-epilepticus
#19
Ukpong B Eyo, Jiyun Peng, Madhuvika Murugan, Mingshu Mo, Almin Lalani, Ping Xie, Pingyi Xu, David J Margolis, Long-Jun Wu
Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imaging in vivo and ex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28093569/translational-evaluation-of-translocator-protein-as-a-marker-of-neuroinflammation-in-schizophrenia
#20
T Notter, J M Coughlin, T Gschwind, U Weber-Stadlbauer, Y Wang, M Kassiou, A C Vernon, D Benke, M G Pomper, A Sawa, U Meyer
Positron emission tomography (PET) imaging with radiotracers that target translocator protein 18 kDa (TSPO) has become a popular approach to assess putative neuroinflammatory processes and associated microglia activation in psychotic illnesses. It remains unclear, however, whether TSPO imaging can accurately capture low-grade inflammatory processes such as those present in schizophrenia and related disorders. Therefore, we evaluated the validity of TSPO as a disease-relevant marker of inflammation using a translational approach, which combined neurodevelopmental and neurodegenerative mouse models with PET imaging in patients with recent-onset schizophrenia and matched controls...
January 17, 2017: Molecular Psychiatry
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