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Inflammasome brain

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https://www.readbyqxmd.com/read/28635590/imbalance-between-innate-antiviral-and-pro-inflammatory-immune-responses-may-contribute-to-different-outcomes-involving-low-and-highly-pathogenic-avian-influenza-h5n3-infections-in-chickens
#1
John Pasick, Sandra Diederich, Yohannes Berhane, Carissa Embury-Hyatt, Wanhong Xu
In order to gain further insight into the early virus-host interactions associated with highly pathogenic avian influenza virus infections in chickens, genome-wide expression profiling of chicken lung and brain was carried out at 24 and 72 h post-inoculation (h p.i.). For this purpose two recombinant H5N3 viruses were utilized, each possessing a polybasic HA0 cleavage site but differing in pathogenicity. The original rH5N3 P0 virus, which has a low-pathogenic phenotype, was passaged six times through chickens to give rise to the derivative rH5N3 P6 virus, which is highly pathogenic (Diederich S, Berhane Y, Embury-Hyatt C, Hisanaga T, Handel K et al...
June 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28630327/virus-induced-inflammasome-activation-is-suppressed-by-prostaglandin-d2-dp1-signaling
#2
Rahul Vijay, Anthony R Fehr, Ann M Janowski, Jeremiah Athmer, Dorthea L Wheeler, Matthew Grunewald, Ramakrishna Sompallae, Samarchith P Kurup, David K Meyerholz, Fayyaz S Sutterwala, Shuh Narumiya, Stanley Perlman
Prostaglandin D2 (PGD2), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD2 signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression analyses indicated that PGD2/DP1 signaling is required for up-regulation of a putative inflammasome inhibitor, PYDC3, in CD11b(+) cells in the CNS of infected mice...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28618410/deletion-of-the-inflammasome-sensor-aim2-mitigates-a%C3%AE-deposition-and-microglial-activation-but-increases-inflammatory-cytokine-expression-in-an-alzheimer-disease-mouse-model
#3
Pei-Jung Wu, Yun-Fen Hung, Hsin-Yu Liu, Yi-Ping Hsueh
OBJECTIVE: Inflammation is clearly associated with Alzheimer disease (AD). Knockout of Nlrp3, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether Aim2 deletion also influences the phenotype of a 5XFAD AD mouse model. METHODS: Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, Aim2-/-, 5XFAD, and Aim2-/-;5XFAD mice...
June 16, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28610608/isoliquiritigenin-alleviates-early-brain-injury-after-experimental-intracerebral-hemorrhage-via-suppressing-ros-and-or-nf-%C3%AE%C2%BAb-mediated-nlrp3-inflammasome-activation-by-promoting-nrf2-antioxidant-pathway
#4
Jun Zeng, Yizhao Chen, Rui Ding, Liang Feng, Zhenghao Fu, Shuo Yang, Xinqing Deng, Zhichong Xie, Shizhong Zheng
BACKGROUND: Intracerebral hemorrhage (ICH) induces potently oxidative stress responses and inflammatory processes. Isoliquiritigenin (ILG) is a flavonoid with a chalcone structure and can activate nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant system, negatively regulate nuclear factor-κB (NF-κB) and nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathways, but its role and potential molecular mechanisms in the pathology following ICH remain unclear...
June 13, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28605578/roflupram-a-phosphodiesterase-4-inhibitior-suppresses-inflammasome-activation-through-autophagy-in-microglial-cells
#5
Tingting You, Yu-Fang Cheng, Jiahong Zhong, Bingtian Bi, Bingqing Zeng, Wenhua Zheng, Hai-Tao Wang, Jiang-Ping Xu
Inhibition of phosphodiesterase 4 (PDE4) suppressed the inflammatory responses in the brain. However, the underlying mechanisms are poorly understood. Roflupram (ROF) is a novel PDE4 inhibitor. In the present study, we found that ROF enhanced the level of microtubule-associated protein 1 light chain 3 II (LC3-II) and decreased p62 in microglial BV-2 cells. Enhanced fluorescent signals were observed in BV-2 cells treated with ROF by Lysotracker red and acridine orange staining. In addition, immunofluorescence indicated a significant increase in punctate LC3...
June 12, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#6
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28596733/melatonin-supplementation-a-strategy-to-prevent-neurological-diseases-through-maintaining-integrity-of-blood-brain-barrier-in-old-people
#7
Wen-Cao Liu, Xiaona Wang, Xinyu Zhang, Xi Chen, Xinchun Jin
Blood brain barrier (BBB) plays a crucial role in maintaining homeostasis of microenvironment that is essential to neural function of the central nervous system (CNS). When facing various extrinsic or intrinsic stimuli, BBB is damaged which is an early event in pathogenesis of a variety of neurological diseases in old patients including acute and chronic cerebral ischemia, Alzheimer's disease and etc. Treatments that could maintain the integrity of BBB may prevent neurological diseases following various stimuli...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28579326/rip1-rip3-drp1-pathway-regulates-nlrp3-inflammasome-activation-following-subarachnoid-hemorrhage
#8
Keren Zhou, Ligen Shi, Zhen Wang, Jingyi Zhou, Anatol Manaenko, Cesar Reis, Sheng Chen, Jianmin Zhang
The NLRP3 inflammasome functions as a crucial component of the inflammatory response in early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanisms underlying the activation of NLRP3 inflammasome has not been well elucidated. In this study, we hypothesized the RIP1-RIP3-DRP1 pathway was involved in the activation of the NLRP3 inflammasome following SAH. SAH was induced by endovascular perforation in rats. Necrostatin-1 (Nec-1) or mitochondrial division inhibitor (Mdivi-1) was administered 1h after SAH by intraperitoneal injection...
June 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28546552/melatonin-mediated-mitophagy-protects-against-early-brain-injury-after-subarachnoid-hemorrhage-through-inhibition-of-nlrp3-inflammasome-activation
#9
Shenglong Cao, Sudeep Shrestha, Jianru Li, Xiaobo Yu, Jingyin Chen, Feng Yan, Guangyu Ying, Chi Gu, Lin Wang, Gao Chen
The NLRP3 inflammasome is activated in the early period following subarachnoid hemorrhage(SAH), resulting in inflammatory responses. Recent studies have shown that activation of NLRP3 inflammasome is suppressed by autophagy, but the potential mechanism is unclear. In this study, we examined whether mitophagy was involved in the beneficial effect of melatonin and its relationship with NLRP3 inflammasome activation after SAH. In total, 130 adult-male SD rats were randomly divided into four groups: sham group, SAH + vehicle group, SAH + melatonin group, and SAH + 3-methyladenine (3-MA) + melatonin group...
May 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28532818/tdp-43-upregulation-mediated-by-the-nlrp3-inflammasome-induces-cognitive-impairment-in-2-2-4-4-tetrabromodiphenyl-ether-bde-47-treated-mice
#10
Juan Zhuang, Xin Wen, Yan-Qiu Zhang, Qun Shan, Zi-Feng Zhang, Gui-Hong Zheng, Shao-Hua Fan, Meng-Qiu Li, Dong-Mei Wu, Bin Hu, Jun Lu, Yuan-Lin Zheng
It is now commonly known that exposure to polybrominated diphenyl ethers (PBDEs) may cause neurotoxicity and cognitive deficits in children as well as adults, but the underlying mechanisms are still not clear. In the present study, we aimed to elucidate the potential underlying mechanism of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity and cognitive impairment. Our results showed that BDE-47-treated mice exhibited impaired cognition and robust upregulation of nuclear TDP-43 in the hippocampus...
May 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28521881/acute-fasting-inhibits-central-caspase-1-activity-reducing-anxiety-like-behavior-and-increasing-novel-object-and-object-location-recognition
#11
Albert E Towers, Maci L Oelschlager, Jay Patel, Stephen J Gainey, Robert H McCusker, Gregory G Freund
BACKGROUND: Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. METHODS: Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28503575/association-between-nlpr1-nlpr3-and-p2x7r-gene-polymorphisms-with-partial-seizures
#12
Haidong Wang, Pengfei Xu, Dehua Liao, Ruili Dang, Xin He, Yujin Guo, Pei Jiang
Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28477436/brain-inflammasomes-in-stroke-and-depressive-disorders-regulation-by-estrogen
#13
REVIEW
Alexander Slowik, Leoni Lammerding, Stefanie Hoffmann, Cordian Beyer
Neuroinflammation is a devastating pathophysiological process which ends up in brain damage and neuronal death. Pathogens, cell fragments and cellular dysfunction trigger inflammatory responses. Irrespective of the cause, inflammasomes are key intracellular multiprotein signaling platforms which sense neuropathological conditions. The activation of inflammasomes leads to the auto-proteolytic cleavage of caspase-1, resulting in the proteolysis of the pro-inflammatory cytokines interleukin (IL)1beta and IL18 into their bioactive forms...
May 6, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28475625/plasmodium-falciparum-histidine-rich-protein-ii-causes-vascular-leakage-and-exacerbates-experimental-cerebral-malaria-in-mice
#14
Priya Pal, Amanda E Balaban, Michael S Diamond, Photini Sinnis, Robyn S Klein, Daniel E Goldberg
A devastating complication of Plasmodium falciparum infection is cerebral malaria, in which vascular leakage and cerebral swelling lead to coma and often death. P. falciparum produces a protein called histidine-rich protein II (HRPII) that accumulates to high levels in the bloodstream of patients and serves as a diagnostic and prognostic marker for falciparum malaria. Using a human cerebral microvascular endothelial barrier model, we previously found that HRPII activates the endothelial cell inflammasome, resulting in decreased integrity of tight junctions and increased endothelial barrier permeability...
2017: PloS One
https://www.readbyqxmd.com/read/28470485/biomarkers-of-suicide-attempt-behavior-towards-a-biological-model-of-risk
#15
REVIEW
Katherin Sudol, J John Mann
PURPOSE OF REVIEW: The rising suicide rate in the USA will not be reversed without improved risk assessment and prevention practices. To date, the best method for clinicians to assess a patient's risk for suicide is screening for past suicide attempts in the patient and their family. However, neuroimaging, genomic, and biochemical studies have generated a body of findings that allow description of an initial heuristic biological model for suicidal behavior that may have predictive value...
June 2017: Current Psychiatry Reports
https://www.readbyqxmd.com/read/28455230/mangiferin-attenuates-blast-induced-traumatic-brain-injury-via-inhibiting-nlrp3-inflammasome
#16
Kaihua Fan, Jie Ma, Wenjing Xiao, Jingmin Chen, Juan Wu, Jiandong Ren, Jun Hou, Yonghe Hu, Jianwen Gu, Botao Yu
There is growing evidence that Mangiferin possess therapeutic benefit during neuroinflammation on various brain injury models due to its anti-inflammatory properties. It is reported that inflammatory plays a crucial role in the pathogenesis of secondary injury induced by the blast-induced traumatic brain injury (bTBI). However, the role of mangiferin in bTBI is yet to be studied. In our study, the potential effect of mangiferin in the duration of bTBI was examined first. Fortunately, the amelioration of cerebral cortex damage was found in rats suffering bTBI after mangiferin administration...
June 1, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28432035/expression-of-pattern-recognition-receptors-and-activation-of-the-non-canonical-inflammasome-pathway-in-brain-pericytes
#17
Ádám Nyúl-Tóth, Mihály Kozma, Péter Nagyőszi, Krisztina Nagy, Csilla Fazakas, János Haskó, Kinga Molnár, Attila E Farkas, Attila G Végh, György Váró, Péter Galajda, Imola Wilhelm, István A Krizbai
Cerebral pericytes are mural cells embedded in the basement membrane of capillaries. Increasing evidence suggests that they play important role in controlling neurovascular functions, i.e. cerebral blood flow, angiogenesis and permeability of the blood-brain barrier. These cells can also influence neuroinflammation which is highly regulated by the innate immune system. Therefore, we systematically tested the pattern recognition receptor expression of brain pericytes. We detected expression of NOD1, NOD2, NLRC5, NLRP1-3, NLRP5, NLRP9, NLRP10 and NLRX mRNA in non-treated cells...
April 18, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28427559/stress-induced-nlrp3-inflammasome-in-human-diseases
#18
Elísabet Alcocer-Gómez, Beatriz Castejón-Vega, Mario D Cordero
Stress is a complex event that induces disturbances to physiological and psychological homeostasis, and it may have a detrimental impact on certain brain and physiological functions. In the last years, a dual role of the stress effect has been studied in order to elucidate the molecular mechanism by which can induce physiological symptoms after psychological stress exposition and vice versa. In this sense, inflammation has been proposed as an important starring. And in the same line, the inflammasome complex has emerged to give responses because of its role of stress sensor...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28414101/autophagy-in-hemorrhagic-stroke-mechanisms-and-clinical-implications
#19
REVIEW
Haiying Li, Jiang Wu, Haitao Shen, Xiyang Yao, Chenglin Liu, S Pianta, J Han, C V Borlongan, Gang Chen
Accumulating evidence advances the critical role of autophagy in brain pathology after stroke. Investigations employing autophagy induction or inhibition using pharmacological tools or autophagy-related gene knockout mice have recently revealed the biological significance of intact and functional autophagy in stroke. Most of the reported cases attest to a pro-survival role for autophagy in stroke, by facilitating removal of damaged proteins and organelles, which can be recycled for energy generation and cellular defenses...
April 13, 2017: Progress in Neurobiology
https://www.readbyqxmd.com/read/28404595/nlr-members-nlrc4-and-nlrp3-mediate-sterile-inflammasome-activation-in-microglia-and-astrocytes
#20
Leslie Freeman, Haitao Guo, Clément N David, W June Brickey, Sushmita Jha, Jenny P-Y Ting
Inflammation in the brain accompanies several high-impact neurological diseases including multiple sclerosis (MS), stroke, and Alzheimer's disease. Neuroinflammation is sterile, as damage-associated molecular patterns rather than microbial pathogens elicit the response. The inflammasome, which leads to caspase-1 activation, is implicated in neuroinflammation. In this study, we reveal that lysophosphatidylcholine (LPC), a molecule associated with neurodegeneration and demyelination, elicits NLRP3 and NLRC4 inflammasome activation in microglia and astrocytes, which are central players in neuroinflammation...
May 1, 2017: Journal of Experimental Medicine
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