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Journal of Neuroinflammation

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https://www.readbyqxmd.com/read/28340587/lymphocytes-have-a-role-in-protection-but-not-in-pathogenesis-during-la-crosse-virus-infection-in-mice
#1
Clayton W Winkler, Lara M Myers, Tyson A Woods, Aaron B Carmody, Katherine G Taylor, Karin E Peterson
BACKGROUND: La Crosse Virus (LACV) is a primary cause of pediatric viral encephalitis in the USA and can result in severe clinical outcomes. Almost all cases of LACV encephalitis occur in children 16 years or younger, indicating an age-related susceptibility. This susceptibility is recapitulated in a mouse model where weanling (3 weeks old or younger) mice are susceptible to LACV-induced disease, and adults (greater than 6 weeks) are resistant. Disease in mice and humans is associated with infiltrating leukocytes to the CNS...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28340583/inflammatory-signature-of-cerebellar-neurodegeneration-during-neonatal-hyperbilirubinemia-in-ugt1-mouse-model
#2
Simone Vodret, Giulia Bortolussi, Jana Jašprová, Libor Vitek, Andrés F Muro
BACKGROUND: Severe hyperbilirubinemia is toxic during central nervous system development. Prolonged and uncontrolled high levels of unconjugated bilirubin lead to bilirubin-induced neurological damage and eventually death by kernicterus. Bilirubin neurotoxicity is characterized by a wide array of neurological deficits, including irreversible abnormalities in motor, sensitive and cognitive functions, due to bilirubin accumulation in the brain. Despite the abundant literature documenting the in vitro and in vivo toxic effects of bilirubin, it is unclear which molecular and cellular events actually characterize bilirubin-induced neurodegeneration in vivo...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28340576/polysaccharides-from-ganoderma-lucidum-attenuate-microglia-mediated-neuroinflammation-and-modulate-microglial-phagocytosis-and-behavioural-response
#3
Qing Cai, Yuanyuan Li, Gang Pei
BACKGROUND: Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28340575/nox2-deficiency-alters-macrophage-phenotype-through-an-il-10-stat3-dependent-mechanism-implications-for-traumatic-brain-injury
#4
James P Barrett, Rebecca J Henry, Sonia Villapol, Bogdan A Stoica, Alok Kumar, Mark P Burns, Alan I Faden, David J Loane
BACKGROUND: NADPH oxidase (NOX2) is an enzyme system that generates reactive oxygen species (ROS) in microglia and macrophages. Excessive ROS production is linked with neuroinflammation and chronic neurodegeneration following traumatic brain injury (TBI). Redox signaling regulates macrophage/microglial phenotypic responses (pro-inflammatory versus anti-inflammatory), and NOX2 inhibition following moderate-to-severe TBI markedly reduces pro-inflammatory activation of macrophages/microglia resulting in concomitant increases in anti-inflammatory responses...
March 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28330482/development-of-a-model-of-saint-louis-encephalitis-infection-and-disease-in-mice
#5
Rafael Elias Marques, Juliana L Del Sarto, Rebeca P F Rocha, Giovanni F Gomes, Allysson Cramer, Milene A Rachid, Danielle G Souza, Maurício L Nogueira, Mauro M Teixeira
BACKGROUND: Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine. METHODS: To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease...
March 22, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28320442/analysis-of-monocyte-infiltration-in-mptp-mice-reveals-that-microglial-cx3cr1-protects-against-neurotoxic-over-induction-of-monocyte-attracting-ccl2-by-astrocytes
#6
Vincent R Parillaud, Guillaume Lornet, Yann Monnet, Anne-Laure Privat, Andrei T Haddad, Vanessa Brochard, Amaury Bekaert, Camille Baudesson de Chanville, Etienne C Hirsch, Christophe Combadière, Stéphane Hunot, Christian S Lobsiger
BACKGROUND: Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2(+) monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death...
March 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28320424/the-alzheimer-s-disease-risk-factors-apolipoprotein-e-and-trem2-are-linked-in-a-receptor-signaling-pathway
#7
Charlotte Jendresen, Vibeke Årskog, Michael R Daws, Lars N G Nilsson
BACKGROUND: Triggering receptor expressed on myeloid cells 2 (TREM2) and apolipoprotein E (APOE) are genetically linked to Alzheimer's disease. Here, we investigated whether human ApoE mediates signal transduction through human and murine TREM2 and sought to identify a TREM2-binding domain in human ApoE. METHODS: To investigate cell signaling through TREM2, a cell line was used which expressed an NFAT-inducible β-galactosidase reporter and human or murine TREM2, fused to CD8 transmembrane and CD3ζ intracellular signaling domains...
March 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28320438/regulatory-t-cell-frequency-but-not-plasma-il-33-levels-represents-potential-immunological-biomarker-to-predict-clinical-response-to-intravenous-immunoglobulin-therapy
#8
Mohan S Maddur, Emmanuel Stephen-Victor, Mrinmoy Das, Praveen Prakhar, Varun K Sharma, Vikas Singh, Magalie Rabin, Jamma Trinath, Kithiganahalli N Balaji, Francis Bolgert, Jean-Michel Vallat, Laurent Magy, Srini V Kaveri, Jagadeesh Bayry
BACKGROUND: Intravenous immunoglobulin (IVIG) is a polyspecific pooled immunoglobulin G preparation and one of the commonly used therapeutics for autoimmune diseases including those of neurological origin. A recent report in murine model proposed that IVIG expands regulatory T (Treg) cells via induction of interleukin 33 (IL-33). However, translational insight on these observations is lacking. METHODS: Ten newly diagnosed Guillain-Barré syndrome (GBS) patients were treated with IVIG at the rate of 0...
March 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28302163/matrix-metalloproteinase-activity-stimulates-n-cadherin-shedding-and-the-soluble-n-cadherin-ectodomain-promotes-classical-microglial-activation
#9
Katherine Conant, Stefano Daniele, P Lorenzo Bozzelli, Tsion Abdi, Amanda Edwards, Arek Szklarczyk, India Olchefske, David Ottenheimer, Kathleen Maguire-Zeiss
BACKGROUND: Matrix metalloproteinases (MMPs) are a family of enzymes that are typically released from intracellular stores to act on specific extracellular substrates. MMP expression and activity can be increased in a neuronal activity-dependent manner, and further increased in response to tissue injury. MMP substrates include cell adhesion molecules (CAMs) that are abundantly expressed in the brain and well positioned for membrane proximal cleavage. Importantly, CAM integrity is important to synaptic structure and axon-myelin interactions, and shed ectodomains may themselves influence cellular function...
March 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28302146/relationship-of-acute-axonal-damage-wallerian-degeneration-and-clinical-disability-in-multiple-sclerosis
#10
Shailender Singh, Tobias Dallenga, Anne Winkler, Shanu Roemer, Brigitte Maruschak, Heike Siebert, Wolfgang Brück, Christine Stadelmann
BACKGROUND: Axonal damage and loss substantially contribute to the incremental accumulation of clinical disability in progressive multiple sclerosis. Here, we assessed the amount of Wallerian degeneration in brain tissue of multiple sclerosis patients in relation to demyelinating lesion activity and asked whether a transient blockade of Wallerian degeneration decreases axonal loss and clinical disability in a mouse model of inflammatory demyelination. METHODS: Wallerian degeneration and acute axonal damage were determined immunohistochemically in the periplaque white matter of multiple sclerosis patients with early actively demyelinating lesions, chronic active lesions, and inactive lesions...
March 17, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28302135/myeloid-c-ebp%C3%AE-deficiency-reshapes-microglial-gene-expression-and-is-protective-in-experimental-autoimmune-encephalomyelitis
#11
Marta Pulido-Salgado, Jose M Vidal-Taboada, Gerardo Garcia Diaz-Barriga, Joan Serratosa, Tony Valente, Paola Castillo, Jonathan Matalonga, Marco Straccia, Josep M Canals, Annabel Valledor, Carme Solà, Josep Saura
BACKGROUND: CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage, but the involvement in this neuroprotective effect of the various C/EBPβ-expressing cell types is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture, we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo...
March 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28302134/microrna-142-regulates-inflammation-and-t-cell-differentiation-in-an-animal-model-of-multiple-sclerosis
#12
Farideh Talebi, Samira Ghorbani, Wing Fuk Chan, Roobina Boghozian, Farimah Masoumi, Sedigheh Ghasemi, Mohammed Vojgani, Christopher Power, Farshid Noorbakhsh
BACKGROUND: MicroRNAs have emerged as an important class of modulators of gene expression. These molecules influence protein synthesis through translational repression or degradation of mRNA transcripts. Herein, we investigated the potential role of miR-142a isoforms, miR-142a-3p and miR-142a-5p, in the context of autoimmune neuroinflammation. METHODS: The expression levels of two mature isoforms of miR-142 were measured in the brains of patients with multiple sclerosis (MS) and the CNS tissues from mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
March 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28292310/microglial-derived-microparticles-mediate-neuroinflammation-after-traumatic-brain-injury
#13
Alok Kumar, Bogdan A Stoica, David J Loane, Ming Yang, Gelareh Abulwerdi, Niaz Khan, Asit Kumar, Stephen R Thom, Alan I Faden
BACKGROUND: Local and systemic inflammatory responses are initiated early after traumatic brain injury (TBI), and may play a key role in the secondary injury processes resulting in neuronal loss and neurological deficits. However, the mechanisms responsible for the rapid expansion of neuroinflammation and its long-term progression have yet to be elucidated. Here, we investigate the role of microparticles (MP), a member of the extracellular vesicle family, in the exchange of pro-inflammatory molecules between brain immune cells, as well as their transfer to the systemic circulation, as key pathways of inflammation propagation following brain trauma...
March 15, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28288671/microglia-derived-il-1%C3%AE-contributes-to-axon-development-disorders-and-synaptic-deficit-through-p38-mapk-signal-pathway-in-septic-neonatal-rats
#14
Qianpeng Han, Qiongyu Lin, Peixian Huang, Mengmeng Chen, Xin Hu, Hui Fu, Shaoru He, Fengcai Shen, Hongke Zeng, Yiyu Deng
BACKGROUND: Axon development plays a pivotal role in the formation of synapse, nodes of Ranvier, and myelin sheath. Interleukin-1β (IL-1β) produced by microglia may cause myelination disturbances through suppression of oligodendrocyte progenitor cell maturation in the septic neonatal rats. Here, we explored if a microglia-derived IL-1β would disturb axon development in the corpus callosum (CC) following lipopolysaccharide (LPS) administration, and if so, whether it is associated with disorder of synapse formation in the cerebral cortex and node of Ranvier...
March 14, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28288663/macrophage-and-nerve-interaction-in-endometriosis
#15
REVIEW
Jinjie Wu, Hongyu Xie, Shuzhong Yao, Yanchun Liang
Dysregulation of the immune system in endometriotic milieus has been considered to play a pivotal role in the pathogenesis of endometriosis. Macrophage recruitment and nerve fiber infiltration are the two major characteristics of this aberrant immune environment. First, the recruitment of macrophages and their polarization phenotype within the endometriotic lesion have been demonstrated to facilitate the development and maintenance of endometriosis. M1 phenotype of macrophages has the capacity to secrete multiple cytokines for inflammatory response, while M2 macrophage possesses an opposite property that can mediate the process of immunosuppression and neuroangiogenesis...
March 14, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28284226/enhanced-susceptibility-of-triple-transgenic-alzheimer-s-disease-3xtg-ad-mice-to-acute-infection
#16
Rebecca Montacute, Kerry Foley, Ruth Forman, Kathryn Jane Else, Sheena Margaret Cruickshank, Stuart McRae Allan
BACKGROUND: Infection is a recognised risk factor for Alzheimer's disease (AD) and can worsen symptoms in established disease. AD patients have higher rates of infection and are more likely to require hospital admissions due to infections than individuals without dementia. Infections have also been found to increase the risk of those over 84 years of age being diagnosed with dementia. However, few studies have investigated immune responses to infection in AD. METHODS: Here, we investigated the immune responses of the triple transgenic Alzheimer's disease (3xTg-AD) mouse model of AD to infection with the parasites Toxoplasma gondii and Trichuris muris...
March 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28284222/teriflunomide-and-monomethylfumarate-target-hiv-induced-neuroinflammation-and-neurotoxicity
#17
Björn Ambrosius, Simon Faissner, Kirsten Guse, Marec von Lehe, Thomas Grunwald, Ralf Gold, Bastian Grewe, Andrew Chan
HIV-associated neurocognitive disorders (HAND) affect about 50% of infected patients despite combined antiretroviral therapy (cART). Ongoing compartmentalized inflammation mediated by microglia which are activated by HIV-infected monocytes has been postulated to contribute to neurotoxicity independent from viral replication. Here, we investigated effects of teriflunomide and monomethylfumarate on monocyte/microglial activation and neurotoxicity. Human monocytoid cells (U937) transduced with a minimal HIV-Vector were co-cultured with human microglial cells (HMC3)...
March 11, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28279172/astrocyte-specific-overexpressed-gene-signatures-in-response-to-methamphetamine-exposure-in-vitro
#18
Nikki Bortell, Liana Basova, Svetlana Semenova, Howard S Fox, Timothy Ravasi, Maria Cecilia G Marcondes
BACKGROUND: Astrocyte activation is one of the earliest findings in the brain of methamphetamine (Meth) abusers. Our goal in this study was to identify the characteristics of the astrocytic acute response to the drug, which may be critical in pathogenic outcomes secondary to the use. METHODS: We developed an integrated analysis of gene expression data to study the acute gene changes caused by the direct exposure to Meth treatment of astrocytes in vitro, and to better understand how astrocytes respond, what are the early molecular markers associated with this response...
March 9, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28264694/cell-specific-deletion-of-c1qa-identifies-microglia-as-the-dominant-source-of-c1q-in-mouse-brain
#19
Maria I Fonseca, Shu-Hui Chu, Michael X Hernandez, Melody J Fang, Lila Modarresi, Pooja Selvan, Grant R MacGregor, Andrea J Tenner
BACKGROUND: The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain. METHODS: To identify the source(s) of C1q in the brain, the C1qa gene was selectively inactivated in the microglia or Thy-1(+) neurons in both wild type mice and a mouse model of Alzheimer's disease (AD), and C1q synthesis assessed by immunohistochemistry, QPCR, and western blot analysis...
March 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28259175/pleiotrophin-regulates-microglia-mediated-neuroinflammation
#20
Rosalía Fernández-Calle, Marta Vicente-Rodríguez, Esther Gramage, Jimena Pita, Carmen Pérez-García, Marcel Ferrer-Alcón, María Uribarri, María P Ramos, Gonzalo Herradón
BACKGROUND: Pleiotrophin (PTN) is a cytokine found highly upregulated in the brain in different disorders characterized by overt neuroinflammation such as neurodegenerative diseases, drug addiction, traumatic injury, and ischemia. In the present work, we have explored whether PTN modulates neuroinflammation and if Toll-like receptor 4 (TLR4), crucial in the initiation of an immune response, is involved. METHODS: In immunohistochemistry assays, we studied lipopolysaccharide (LPS, 7...
March 4, 2017: Journal of Neuroinflammation
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