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Inflammasome microglia

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https://www.readbyqxmd.com/read/29439605/microglial-inflammasome-activation-in-penetrating-ballistic-like-brain-injury
#1
Stephanie W Lee, Shyam Gajavelli, Markus S Spurlock, Cody Andreoni, Juan Pablo de Rivero Vaccari, M Ross Bullock, Robert W Keane, W Dalton Dietrich
Penetrating traumatic brain injury (PTBI) is a significant cause of death and disability in the United States. Inflammasomes are one of the key regulators of the interleukin (IL)-1β mediated inflammatory responses after traumatic brain injury (TBI). However, the contribution of inflammasome signaling after PTBI has not been determined. In this study, adult male Sprague-Dawley rats were subjected to sham procedures or penetrating ballistic-like brain injury (PBBI) and sacrificed at various time points. Tissues were assessed by immunoblot analysis for expression of IL-1β, IL-18 and components of the inflammasome: apoptosis-associated speck-like protein containing a caspase-activation and recruitment domain (ASC), caspase-1, X-linked inhibitor of apoptosis protein (XIAP), NOD-like receptor protein 3 (NLRP3), and gasdermin-D (GSDMD)...
February 14, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29434227/the-nlrp3-inflammasome-may-contribute-to-pathologic-neovascularization-in-the-advanced-stages-of-diabetic-retinopathy
#2
Shyam S Chaurasia, Rayne R Lim, Bhav H Parikh, Yeo Sia Wey, Bo Bo Tun, Tien Yin Wong, Chi D Luu, Rupesh Agrawal, Arkasubhra Ghosh, Alessandra Mortellaro, Elizabeth Rackoczy, Rajiv R Mohan, Veluchamy A Barathi
Diabetic retinopathy (DR) is a retinal microvascular disease characterized by inflammatory and angiogenic pathways. In this study, we evaluated NLRP3 inflammasome in a double transgenic mouse model, Akimba (Ins2 Akita xVEGF +/- ), which demonstrates hyperglycemia, vascular hyperpermeability and neovascularization seen in the proliferative DR. Retinal structural integrity, vascular leakage and function were examined by fundus photography, fluorescein angiography, optical coherence tomography, retinal flat mounts, laser speckle flowgraphy (LSFG), and electroretinography in Akimba and its parental strains, Akita (Ins2 Akita ) and Kimba (trVEGF029) mice...
February 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29396515/blockade-of-microglial-adenosine-a2a-receptor-impacts-inflammatory-mechanisms-reduces-arpe-19-cell-dysfunction-and-prevents-photoreceptor-loss-in-vitro
#3
M H Madeira, K Rashid, A F Ambrósio, A R Santiago, T Langmann
Age-related macular degeneration (AMD) is characterized by pathological changes in the retinal pigment epithelium (RPE) and loss of photoreceptors. Growing evidence has demonstrated that reactive microglial cells trigger RPE dysfunction and loss of photoreceptors, and inflammasome pathways and complement activation contribute to AMD pathogenesis. We and others have previously shown that adenosine A2A receptor (A2AR) blockade prevents microglia-mediated neuroinflammatory processes and mediates protection to the retina...
February 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29343269/microglial-activation-mediates-chronic-mild-stress-induced-depressive-and-anxiety-like-behavior-in-adult-rats
#4
Ya-Lin Wang, Qiu-Qin Han, Wen-Qing Gong, Dong-Hui Pan, Li-Zheng Wang, Wei Hu, Min Yang, Bing Li, Jin Yu, Qiong Liu
BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. METHODS: We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS)...
January 17, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29318480/rosmarinic-acid-mitigates-lipopolysaccharide-induced-neuroinflammatory-responses-through-the-inhibition-of-tlr4-and-cd14-expression-and-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#5
Yicong Wei, Jianxiong Chen, Yonghong Hu, Wei Lu, Xiaoqin Zhang, Ruiguo Wang, Kedan Chu
The excessive activation of microglia plays a key role in the pathogenesis of neurodegenerative diseases. The neuroprotective properties of rosmarinic acid have been reported in a variety of disease models both in vitro and in vivo; however, the mechanism underlying its anti-neuroinflammatory activity has not been clearly elucidated. In the present study, we evaluated the anti-inflammatory effects of rosmarinic acid in conditions of neuroinflammatory injury in vitro and in vivo. The results indicated that rosmarinic acid reduced the expression of CD11b, a marker of microglia and macrophages, in the brain and dramatically inhibited the levels of inflammatory cytokines and mediators, such as TNFα, IL-6, IL-1β, COX-2, and iNOS, in a dose-dependent manner both in vitro and in vivo...
January 9, 2018: Inflammation
https://www.readbyqxmd.com/read/29306934/gliotransmitters-and-cytokines-in-the-control-of-blood-brain-barrier-permeability
#6
REVIEW
Elena D Osipova, Oxana V Semyachkina-Glushkovskaya, Andrey V Morgun, Natalia V Pisareva, Natalia A Malinovskaya, Elizaveta B Boitsova, Elena A Pozhilenkova, Olga A Belova, Vladimir V Salmin, Tatiana E Taranushenko, Mami Noda, Alla B Salmina
The contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions...
January 8, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29304864/hypercapnia-induces-il-1%C3%AE-overproduction-via-activation-of-nlrp3-inflammasome-implication-in-cognitive-impairment-in-hypoxemic-adult-rats
#7
Hong-Guang Ding, Yi-Yu Deng, Ren-Qiang Yang, Qiao-Sheng Wang, Wen-Qiang Jiang, Yong-Li Han, Lin-Qiang Huang, Miao-Yun Wen, Wen-Hong Zhong, Xu-Sheng Li, Fan Yang, Hong-Ke Zeng
BACKGROUND: Cognitive impairment is one of common complications of acute respiratory distress syndrome (ARDS). Increasing evidence suggests that interleukin-1 beta (IL-1β) plays a role in inducing neuronal apoptosis in cognitive dysfunction. The lung protective ventilatory strategies, which serve to reduce pulmonary morbidity for ARDS patients, almost always lead to hypercapnia. Some studies have reported that hypercapnia contributes to the risk of cognitive impairment and IL-1β secretion outside the central nervous system (CNS)...
January 5, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29301581/activation-of-dopamine-d1-receptor-decreased-nlrp3-mediated-inflammation-in-intracerebral-hemorrhage-mice
#8
Tian Wang, Derek Nowrangi, Lingyan Yu, Tai Lu, Jiping Tang, Bing Han, Yuxin Ding, Fenghua Fu, John H Zhang
BACKGROUND: Inflammasomes are involved in diverse inflammatory diseases. Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition. METHODS: One hundred and six male CD-1 mice were subjected to intrastriatal injection of bacterial collagenase or PBS...
January 4, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29290552/microglial-ramification-surveillance-and-interleukin-1%C3%AE-release-are-regulated-by-the-two-pore-domain-k-channel-thik-1
#9
Christian Madry, Vasiliki Kyrargyri, I Lorena Arancibia-Cárcamo, Renaud Jolivet, Shinichi Kohsaka, Robert M Bryan, David Attwell
Microglia exhibit two modes of motility: they constantly extend and retract their processes to survey the brain, but they also send out targeted processes to envelop sites of tissue damage. We now show that these motility modes differ mechanistically. We identify the two-pore domain channel THIK-1 as the main K+ channel expressed in microglia in situ. THIK-1 is tonically active, and its activity is potentiated by P2Y12 receptors. Inhibiting THIK-1 function pharmacologically or by gene knockout depolarizes microglia, which decreases microglial ramification and thus reduces surveillance, whereas blocking P2Y12 receptors does not affect membrane potential, ramification, or surveillance...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29273951/neuroinflammatory-responses-in-alzheimer-s-disease
#10
REVIEW
Cira Dansokho, Michael Thomas Heneka
Neuroinflammatory responses in Alzheimer's disease (AD) are complex and not fully understood. They involve various cellular and molecular players and associate interaction between the central nervous system (CNS) and the periphery. Amyloid peptides within the senile plaques and abnormally phosphorylated tau in neurofibrillary tangles are able to initiate inflammatory responses, in brain of AD patients and in mouse models of this disease. The outcome of these responses on the pathophysiology of AD depends on several factors and can be either beneficial or detrimental...
December 22, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29219210/bioenergetic-regulation-of-microglia
#11
REVIEW
Soumitra Ghosh, Erika Castillo, Elma S Frias, Raymond A Swanson
Microglia have diverse actions, ranging from synapse pruning in development to cytotoxic effects in disease. Brain energy metabolism and substrate availability vary under normal and disease states, but how these variations influence microglial function is relatively unknown. Microglia, like most other cell types, express the full complement of gene products required for both glycolytic and oxidative metabolism. Evidence suggests that microglia increase aerobic glycolysis and decrease respiration when activated by various stimuli...
December 8, 2017: Glia
https://www.readbyqxmd.com/read/29212744/selective-nlrp3-pyrin-domain-containing-protein-3-inflammasome-inhibitor-reduces-brain-injury-after-intracerebral-hemorrhage
#12
Honglei Ren, Ying Kong, Zhijia Liu, Dongyun Zang, Xiaoxia Yang, Kristofer Wood, Minshu Li, Qiang Liu
BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a devastating disease without effective treatment. As a key component of the innate immune system, the NOD-like receptor (NLR) family, NLRP3 (pyrin domain-containing protein 3) inflammasome, when activated after ICH, promotes neuroinflammation and brain edema. MCC950 is a potent, selective, small-molecule NLRP3 inhibitor that blocks NLRP3 activation at nanomolar concentrations. Here, we examined the effect of MCC950 on brain injury and inflammation in 2 models of ICH in mice...
December 6, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29196167/cathepsin-b-links-oxidative-stress-to-the-activation-of-nlrp3-inflammasome
#13
Hua Bai, Bo Yang, Wenfeng Yu, Yan Xiao, Dejun Yu, Qifang Zhang
Oxidative stress-mediated activation of NLRP3 inflammasome in microglia is critical in the development of neurodegerative diseases such as Alzheimer's disease (AD), Parkinson disease (PD). However, the mechanism underlying oxidative stress activates NLRP3 inflammasome remains exclusive. Here we demonstrated cathepsin B (CTSB) as a regulator of the activation of NLRP3 inflammasome by H2O2. H2O2 induced IL-1β secretion in NLRP3 inflammasome-dependent manner. H2O2 treatment increased CTSB activity, which in turn activated NLRP3 inflammasome, and subsequently processed pro-caspase-1 cleavage into caspase-1, resulting in IL-1 β secretion...
November 28, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29191728/the-sp2-iminosugar-glycolipid-1-dodecylsulfonyl-5n-6o-oxomethylidenenojirimycin-dso2-onj-as-selective-anti-inflammatory-agent-by-modulation-of-hemeoxygenase-1-in-bv-2-microglial-cells-and-retinal-explants
#14
Elena Alcalde-Estévez, Ana I Arroba, Elena M Sánchez-Fernández, Carmen Ortiz Mellet, Jose M García Fernández, Laura Masgrau, Ángela M Valverde
Neuroinflammation is an early event during diabetic retinopathy (DR) that impacts the dynamics of microglia polarization. Gliosis is a hallmark of DR and we have reported the beneficial effects of 1R-DSO-ONJ, a member of the sp2-iminosugar glycolipid (sp2-IGL) family, in targeting microglia and reducing gliosis in diabetic db/db mice. Herein, we analyzed the effect of DSO2-ONJ, another family compound incorporating a sulfone group that better mimics the phosphate group of phosphatidylinositol ether lipid analogues (PIAs), in Bv...
November 27, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29178967/blocking-atp-sensitive-potassium-channel-alleviates-morphine-tolerance-by-inhibiting-hsp70-tlr4-nlrp3-mediated-neuroinflammation
#15
Jie Qu, Xue-You Tao, Peng Teng, Yan Zhang, Ci-Liang Guo, Liang Hu, Yan-Ning Qian, Chun-Yi Jiang, Wen-Tao Liu
BACKGROUND: Long-term use of morphine induces analgesic tolerance, which limits its clinical efficacy. Evidence indicated morphine-evoked neuroinflammation mediated by toll-like receptor 4 (TLR4) - NOD-like receptor protein 3 (NLRP3) inflammasome was important for morphine tolerance. In our study, we investigated whether other existing alternative pathways caused morphine-induced activation of TLR4 in microglia. We focused on heat shock protein 70 (HSP70), a damage-associated molecular pattern (DAMP), which was released from various cells upon stimulations under the control of KATP channel and bound with TLR4-inducing inflammation...
November 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29173188/innate-immune-surveillance-in-the-central-nervous-system-in-legionella-pneumophila-infection
#16
Pasqualina Lagana, Luca Soraci, Maria Elsa Gambuzza, Santi Delia
Innate immune response represents a common event in many neuroinflammatory diseases. The resident immune cells of the central nervous system (CNS) are capable of sensing and reacting to both infections and sterile trauma. Peripheral immune cell migration into CNS is regulated by the blood-brain barrier (BBB), although peripheral immune cells can invade CNS through meninges, choroid plexus, perivascular spaces, and cerebrospinal fluid. Consequently, in the brain immune reactions can be mediated by both resident and peripheral immune cells...
November 23, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29163015/resveratrol-attenuates-early-brain-injury-after-experimental-subarachnoid-hemorrhage-via-inhibition-of-nlrp3-inflammasome-activation
#17
Xiangsheng Zhang, Qi Wu, Qingrong Zhang, Yue Lu, Jingpeng Liu, Wei Li, Shengyin Lv, Mengliang Zhou, Xin Zhang, Chunhua Hang
Previous studies have demonstrated resveratrol (RSV) has beneficial effects in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the beneficial effects of RSV and the underlying mechanisms have not been clearly identified. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation plays a crucial role in the EBI pathogenesis. The aim of this study was to investigate the role of RSV on the NLRP3 inflammasome signaling pathway and EBI in rats after SAH...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29111328/3-naphthalen-2-yl-propoxy-methyl-azetidine-hydrochloride-attenuates-nlrp3-inflammasome-mediated-signaling-pathway-in-lipopolysaccharide-stimulated-bv2-microglial-cells
#18
Ji Woong Yang, Seung-Ju Yang, Jung-Min Na, Hoh-Gyu Hahn, Sung-Woo Cho
The nucleotide-binding and oligomerization domain-like receptor containing a pyrin domain 3 (NLRP3) inflammasome is a multiprotein complex with a role in innate immune responses. NLRP3 inflammasome dysfunction is a common feature of chronic inflammatory diseases. Microglia activation is also associated with neuroinflammatory pathologies. We previously reported that 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792) reduced hypoxia-induced toxicity by modulating inflammation. However, no studies have elucidated the precise mechanisms for the anti-inflammatory action of KHG26792, in particular via inflammasome mediation...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29070054/targeting-the-nlrp3-inflammasome-to-attenuate-spinal-cord-injury-in-mice
#19
Wu Jiang, Maoqiang Li, Fan He, Shaobo Zhou, Liulong Zhu
BACKGROUND: Spinal cord injury (SCI) is a devastating disease, which results in tissue loss and neurologic dysfunction. NLRP3 inflammasome plays an important role in the mechanism of diverse diseases. However, no studies have demonstrated the role of NLRP3 inflammasome and the effects of NLRP3 inflammasome inhibitors in a mouse model of SCI. We investigated whether inhibition of NLRP3 inflammasome activation by the pharmacologic inhibitor BAY 11-7082 or A438079 could exert neuroprotective effects in a mouse model of SCI...
October 25, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29067455/hyperbaric-oxygen-alleviates-the-activation-of-nlrp%C3%A2-3%C3%A2-inflammasomes-in-traumatic-brain-injury
#20
Huihui Qian, Qinghe Li, Woda Shi
Growing evidence has demonstrated that the nucleotide‑binding oligomerization domain‑like receptor family pyrin domain containing 3 (NLRP‑3) inflammasome‑mediated inflammatory pathways have been involved in the secondary injury of traumatic brain injury (TBI). In the present study, the authors investigated the effects of hyperbaric oxygen (HBO) therapy on the NLRP‑3 inflammasome pathway following TBI. Following the evaluation of motor deficits and brain edema, the therapeutic effects of HBO on interleukin (IL)‑1β and IL‑18 expression were assessed, as well as NLRP‑3 inflammasome activation following TBI...
October 2017: Molecular Medicine Reports
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