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Yue Lu, Xiang-Sheng Zhang, Zi-Huan Zhang, Xiao-Ming Zhou, Yong-Yue Gao, Guang-Jie Liu, Han Wang, Ling-Yun Wu, Wei Li, Chun-Hua Hang
BACKGROUND: Peroxiredoxin (Prx) protein family have been reported as important damage-associated molecular patterns (DAMPs) in ischemic stroke. Since peroxiredoxin 2 (Prx2) is the third most abundant protein in erythrocytes and the second most protein in the cerebrospinal fluid in traumatic brain injury and subarachnoid hemorrhage (SAH) patients, we assessed the role of extracellular Prx2 in the context of SAH. METHODS: We introduced a co-culture system of primary neurons and microglia...
March 19, 2018: Journal of Neuroinflammation
Csaba Fekete, Csaba Vastagh, Ádám Dénes, Erik Hrabovszky, Gábor Nyiri, Imre Kalló, Zsolt Liposits, Miklós Sárvári
Microglia are instrumental for recognition and elimination of amyloid β1-42 oligomers (AβO), but the long-term consequences of AβO-induced inflammatory changes in the brain are unclear. Here, we explored microglial responses and transciptome-level inflammatory signatures in the rat hippocampus after chronic AβO challenge. Middle-aged Long Evans rats received intracerebroventricular infusion of AβO or vehicle for 4 weeks, followed by treatment with artificial CSF or MCC950 for the subsequent 4 weeks. AβO infusion evoked a sustained inflammatory response including activation of NF-κB, triggered microglia activation and increased the expression of pattern recognition and phagocytic receptors...
March 6, 2018: Neuroscience
Federico Colombo, Mattia Bastoni, Annamaria Nigro, Paola Podini, Annamaria Finardi, Giacomo Casella, Menon Ramesh, Cinthia Farina, Claudia Verderio, Roberto Furlan
Microvesicles (MVs) are membrane particles of 200-500 nm released by all cell types constitutively. MVs of myeloid origin are found increased in the cerebrospinal fluid (CSF) of patients suffering from neuroinflammatory disorders, although the factors triggering their production have never been defined. Here, we report that both pro- and anti-inflammatory cytokines, specifically interferon-γ and interleukin-4, are equally able to stimulate the production of MVs from microglia cells and monocytes. Additionally, we found this process to be independent from the best characterized molecular pathway so far described for membrane shedding, which is centered on the purinergic receptor P2X7, whose activation by high concentrations of extracellular ATP (exATP) results in membrane blebbing operated by the secreted enzyme acid sphingomyelinase (ASMase)...
2018: Frontiers in Immunology
Nicolau Beckmann, Elisa Giorgetti, Anna Neuhaus, Stefan Zurbruegg, Nathalie Accart, Paul Smith, Julien Perdoux, Ludovic Perrot, Mark Nash, Sandrine Desrayaud, Peter Wipfli, Wilfried Frieauff, Derya R Shimshek
Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system (CNS). While multiple effective immunomodulatory therapies for MS exist today, they lack the scope of promoting CNS repair, in particular remyelination. Microglia play a pivotal role in regulating myelination processes, and the colony-stimulating factor 1 (CSF-1) pathway is a key regulator for microglia differentiation and survival. Here, we investigated the effects of the CSF-1 receptor kinase inhibitor, BLZ945, on central myelination processes in the 5-week murine cuprizone model by non-invasive and longitudinal magnetic resonance imaging (MRI) and histology...
February 15, 2018: Acta Neuropathologica Communications
Martin Olsson, Johan Ärlig, Jan Hedner, Kaj Blennow, Henrik Zetterberg
Study Objective: To investigate the cumulative effect of 5 consecutive nights of partial sleep deprivation on a panel of cerebrospinal fluid (CSF) biomarkers in healthy adults. Methods: A randomized, cross-over study conducted at the University of Gothenburg. The participants (N=13) were healthy adults (20-40 years of age) with a normal sleeping pattern. The participants underwent a baseline sleep period consisting of 5 nights with 8h spent in bed. A subsequent period with partial sleep deprivation (PSD) consisted of 5 nights of maximum 4h of sleep per night...
February 7, 2018: Sleep
Yuh-Feng Lin, Tsung-Ta Liu, Chou-Hui Hu, Chun-Chi Chen, Jia-Yi Wang
Despite growing evidence that cytokines and chemokines are expressed in humans and rats after heat stress, the cellular mechanisms underlying the effects on the brain after heatstroke (HS) are not fully understood. In this study, we observed time course changes of chemokines in rat brain tissues and elucidated what kinds of cortical cells were affected after HS. Male SD rats were anesthetized and randomly separated into two groups as follows: (a) normothermic sham and (b) HS rats. Rats were sacrificed at different time points (0, 1, 3, 6, and 12h after heat exposure, n=5 in each group) to the end of the experiment in order to extract the mRNA/proteins of cortical tissues...
January 29, 2018: Journal of Neuroimmunology
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...
March 2018: Pain
Sigrid Ottestad-Hansen, Qiu Xiang Hu, Virgine Veronique Follin-Arbelet, Eduard Bentea, Hideyo Sato, Ann Massie, Yun Zhou, Niels Christian Danbolt
The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes...
January 19, 2018: Glia
Teresa Trotta, Maria Antonietta Panaro, Antonia Cianciulli, Giorgio Mori, Adriana Di Benedetto, Chiara Porro
Extracellular vesicles (EVs), based on their origin or size, can be classified as apoptotic bodies, microvesicles (MVs)/microparticles (MPs), and exosomes. EVs are one of the new emerging modes of communication between cells that are providing new insights into the pathophysiology of several diseases. EVs released from activated or apoptotic cells contain specific proteins (signaling molecules, receptors, integrins, cytokines), bioactive lipids, nucleic acids (mRNA, miRNA, small non coding RNAs, DNA) from their progenitor cells...
January 3, 2018: Biochemical Pharmacology
Violetta Refolo, Francesco Bez, Alexia Polissidis, Daniela Kuzdas-Wood, Edith Sturm, Martina Kamaratou, Werner Poewe, Leonidas Stefanis, M Angela Cenci, Marina Romero-Ramos, Gregor K Wenning, Nadia Stefanova
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder characterized by widespread oligodendroglial cytoplasmic inclusions of filamentous α-synuclein, and neuronal loss in autonomic centres, basal ganglia and cerebellar circuits. It has been suggested that primary oligodendroglial α-synucleinopathy may represent a trigger in the pathogenesis of MSA, but the mechanisms underlying selective vulnerability and disease progression are unclear. The post-mortem analysis of MSA brains provides a static final picture of the disease neuropathology, but gives no clear indication on the sequence of pathogenic events in MSA...
January 3, 2018: Acta Neuropathologica Communications
Jaime Imitola, Javad Rasouli, Fumihiro Watanabe, Kader Mahajan, Aswhini D Sharan, Bogoljub Ciric, Guang-Xian Zhang, Abdolmohamad Rostami
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease that disproportionately affects young adults, leading to disability and high costs to society. Infiltration of T cells and monocytes into the central nervous system (CNS) is critical for disease initiation and progression. However, despite a great deal of effort the molecular mechanisms by which immune cells initiate and perpetuate CNS damage in MS have not yet been elucidated. In experimental autoimmune encephalomyelitis (EAE), an animal model of MS, granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by pathogenic Th1 and Th17 cells is critical for the recruitment of monocytes into the CNS during the initial stage of disease...
December 22, 2017: Journal of Neuroimmunology
Xiaolan Li, Huishu Liu, Yuanyuan Yang
Eclampsia is characterized by high morbidity and mortality wordwide. Magnesium sulfate ( MgSO4 ) is used frequently as a prophylaxis for eclamptic seizure in clinical settings. However, the underlying mechanism is less studied, we have previously demonstrated that MgSO4 pretreatment decreases eclampsia-like seizure threshold. Here, we further evaluated the hypothesis that MgSO4 exert neuroprotective actions in eclampsia-like rats model by ameliorating neuroinflammation and brain edema. In this study, the eclampsia-like model was established by administering lipopolysaccharide plus pentylenetetrazol in pregnant Sprague-Dawley rats...
December 27, 2017: Behavioural Brain Research
Natalia Rodríguez, Astrid Morer, E Azucena González-Navarro, Carles Serra-Pages, Daniel Boloc, Teresa Torres, Susana García-Cerro, Sergi Mas, Patricia Gassó, Luisa Lázaro
BACKGROUND: Although the exact etiology of obsessive-compulsive disorder (OCD) is unknown, there is growing evidence of a role for immune dysregulation in the pathophysiology of the disease, especially in the innate immune system including the microglia. To test this hypothesis, we studied inflammatory markers in monocytes from pediatric patients with OCD and from healthy controls. METHODS: We determined the percentages of total monocytes, CD16+ monocytes, and classical (CD14high CD16-), intermediate (CD14high CD16low ), and non-classical (CD14low CD16high ) monocyte subsets in 102 patients with early-onset OCD and in 47 healthy controls...
December 28, 2017: Journal of Neuroinflammation
N Gorlé, C Blaecher, E Bauwens, C Vandendriessche, S Balusu, J Vandewalle, C Van Cauwenberghe, E Van Wonterghem, G Van Imschoot, C Liu, R Ducatelle, C Libert, F Haesebrouck, A Smet, R E Vandenbroucke
Several studies suggest a link between shifts in gut microbiota and neurological disorders. Recently, we reported a high prevalence of Helicobacter suis (H. suis) in patients with Parkinson's disease. Here, we evaluated the effect of gastric H. suis infection on the brain in mice. One month of infection with H. suis resulted in increased brain inflammation, reflected in activation of microglia and cognitive decline. Additionally, we detected choroid plexus inflammation and disruption of the epithelial blood-cerebrospinal fluid (CSF) barrier upon H...
December 16, 2017: Brain, Behavior, and Immunity
Ronen Reshef, Elena Kudryavitskaya, Haran Shani-Narkiss, Batya Isaacson, Neta Rimmerman, Adi Mizrahi, Raz Yirmiya
Microglia play important roles in perinatal neuro- and synapto-genesis. To test the role of microglia in these processes during adulthood, we examined the effects of microglia depletion, via treatment of mice with the CSF-1 receptor antagonist PLX5622, and abrogated neuronal-microglial communication in CX3C receptor-1 deficient (Cx3cr1-/-) mice. Microglia depletion significantly lowered spine density in young (developing) but not mature adult-born-granule-cells (abGCs) in the olfactory bulb. Two-photon time-lapse imaging indicated that microglia depletion reduced spine formation and elimination...
December 18, 2017: ELife
Chong Xie, Xing Li, Xiajun Zhou, Zezhi Li, Yuan Zhang, Li Zhao, Yong Hao, Guang-Xian Zhang, Yangtai Guan
Bone marrow-derived neural stem cells (BM-NSCs) have therapeutic effect on EAE, an animal model of multiple sclerosis. However, the beneficial effect is suboptimal due to the limited immunomodulatory capacity of these cells. In this study, we engineered BM-NSCs with inducible TGFβ1, a potent immunosuppressive cytokine, to enhance their anti-inflammatory capacity. We found that i.v. injected TGFβ1-BM-NSCs more effectively suppressed clinical severity, inflammation and demyelination of the central nervous system of EAE mice...
December 5, 2017: Brain, Behavior, and Immunity
Giovanna Pepe, Marcella De Maglie, Lucia Minoli, Alessandro Villa, Adriana Maggi, Elisabetta Vegeto
BACKGROUND: Microglia are resident myeloid cells of the central nervous system (CNS) that are maintained by self-renewal and actively participate in tissue homeostasis and immune defense. Under the influence of endogenous or pathological signals, microglia undertake biochemical transformations that are schematically classified as the pro-inflammatory M1 phenotype and the alternatively activated M2 state. Dysregulated proliferation of M1-activated microglia has detrimental effects, while an increased number of microglia with the alternative, pro-resolving phenotype might be beneficial in brain pathologies; however, the proliferative response of microglia to M2 signals is not yet known...
December 4, 2017: Journal of Neuroinflammation
Petra Steinacker, Federico Verde, Lubin Fang, Emily Feneberg, Patrick Oeckl, Sigrun Roeber, Sarah Anderl-Straub, Adrian Danek, Janine Diehl-Schmid, Klaus Fassbender, Klaus Fliessbach, Hans Foerstl, Armin Giese, Holger Jahn, Jan Kassubek, Johannes Kornhuber, G Bernhard Landwehrmeyer, Martin Lauer, Elmar Hans Pinkhardt, Johannes Prudlo, Angela Rosenbohm, Anja Schneider, Matthias L Schroeter, Hayrettin Tumani, Christine A F von Arnim, Jochen Weishaupt, Patrick Weydt, Albert C Ludolph, Deniz Yilmazer Hanke, Markus Otto
OBJECTIVES: Neurochemical markers of amyotrophic lateral sclerosis (ALS) that reflect underlying disease mechanisms might help in diagnosis, staging and prediction of outcome. We aimed at determining the origin and differential diagnostic and prognostic potential of the putative marker of microglial activation chitotriosidase (CHIT1). METHODS: Altogether 316 patients were included, comprising patients with sporadic ALS, ALS mimics (disease controls (DCo)), frontotemporal lobar degeneration (FTLD), Creutzfeldt-Jakob disease (CJD), Alzheimer's disease (AD), Parkinson's disease (PD) and healthy controls (Con)...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
Alpdogan Kantarci, Nurgul Aytan, Iro Palaska, Danielle Stephens, Leah Crabtree, Claudia Benincasa, Bruce G Jenkins, Isabel Carreras, Alpaslan Dedeoglu
Dysfunction in the resolution of inflammation may play a key role in Alzheimer's disease (AD). In this study, we found that the levels of specialized pro-resolving lipid mediators (SPMs) in the hippocampus of 5xFAD mice are significantly lower than in non-transgenic littermates. We, therefore, tested the hypothesis that treatment with resolvin E1 (RvE1) and lipoxin A4 (LXA4) alone or in combination will reverse the neuroinflammatory process and decrease Aβ pathology. 5xFAD mice were treated intraperitoneally starting at 1month of age with RvE1 or LXA4 alone or in combination at a dose of 1...
February 2018: Experimental Neurology
Liang Mao, Wei Gao, Shurui Chen, Ying Song, Changwei Song, Zipeng Zhou, Haosen Zhao, Kang Zhou, Wei Wang, Kunming Zhu, Chang Liu, Xifan Mei
The microtubule-stabilizing drug epothilone B (epoB) has shown potential value in the treatment of spinal cord injury (SCI) through diverse mechanisms. However, it remains elusive why a limited overall effect was observed. We aim to investigate the limiting factors underlying functional recovery promoted by epoB. The same SCI model treated by epoB was established as discussed previously. We used a cerebrospinal fluid (CSF) sample to assess the changes in cytokines in milieu of the SCI lesion site after epoB treatment...
November 2, 2017: Cell Death & Disease
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