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https://www.readbyqxmd.com/read/28346613/protective-effect-of-met12-a-small-peptide-inhibitor-of-fas-on-the-retinal-pigment-epithelium-and-photoreceptor-after-sodium-iodate-injury
#1
Jianhui Xiao, Jingyu Yao, Lin Jia, Chengmao Lin, David N Zacks
Purpose: A major problem in macular degeneration is the inability to reduce RPE and photoreceptor death. These cells die by necroptosis and apoptosis, respectively, but the upstream activator(s) of these death pathways is unknown. In this study, we use the sodium iodate (NaIO3) model of oxidative stress to test the hypothesis that activation of the Fas receptor contributes to the death of the RPE and photoreceptors. Methods: Sodium iodate was injected in Brown-Norway rats via femoral vein injection...
March 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28346397/the-process-and-regulatory-components-of-inflammation-in-brain-oncogenesis
#2
REVIEW
A G M Mostofa, Surendra R Punganuru, Hanumantha Rao Madala, Mohammad Al-Obaide, Kalkunte S Srivenugopal
Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers...
March 27, 2017: Biomolecules
https://www.readbyqxmd.com/read/28346104/bioengineered-3d-glial-cell-culture-systems-and-applications-for-neurodegeneration-and-neuroinflammation
#3
P Marc D Watson, Edel Kavanagh, Gary Allenby, Matthew Vassey
Neurodegeneration and neuroinflammation are key features in a range of chronic central nervous system (CNS) diseases such as Alzheimer's and Parkinson's disease, as well as acute conditions like stroke and traumatic brain injury, for which there remains significant unmet clinical need. It is now well recognized that current cell culture methodologies are limited in their ability to recapitulate the cellular environment that is present in vivo, and there is a growing body of evidence to show that three-dimensional (3D) culture systems represent a more physiologically accurate model than traditional two-dimensional (2D) cultures...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345586/new-insights-into-mononuclear-phagocyte-biology-from-the-visual-system
#4
REVIEW
Nancy J Reyes, Emily G O'Koren, Daniel R Saban
Major advances in mononuclear phagocyte biology have been made but key questions pertinent to their roles in health and disease remain, including in the visual system. One problem concerns how dendritic cells can trigger immune responses from certain tightly regulated immune- privileged sites of the eye. Another, albeit separate, problem involves whether there are functional specializations for microglia versus monocytes in retinal neurodegeneration. In this Review, we examine novel insights in eye immune privilege and, separately, we discuss recent inroads concerning retinal degeneration...
March 27, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28343297/association-of-the-cx3cr1-v249i-variant-with-neurofibrillary-pathology-progression-in-late-onset-alzheimer-s-disease
#5
Alan López-López, Ellen Gelpi, Diana Maria Lopategui, Jose M Vidal-Taboada
Neuroinflammation and microglial dysfunction have a prominent role in the pathogenesis of late-onset Alzheimer's disease (LOAD). CX3CR1 is a microglia-specific gene involved in microglia-neuron crosstalk and neuroinflammation. Numerous evidence show the involvement of CX3CR1 in AD. The aim of this study was to investigate if some functional genetic variants of this gene could influence on LOAD's outcome, in a neuropathologically confirmed Spanish cohort. We designed an open, pragmatic, case-control retrospective study including a total of 475 subjects (205 pathologically confirmed AD cases and 270 controls)...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28343295/identification-of-sphingosine-1-phosphate-receptor-subtype-1-s1p1-as-a-pathogenic-factor-in-transient-focal-cerebral-ischemia
#6
Bhakta Prasad Gaire, Chi-Ho Lee, Arjun Sapkota, Sang Yeul Lee, Jerold Chun, Hee Jun Cho, Tae-Gyu Nam, Ji Woong Choi
Medically relevant roles of receptor-mediated sphingosine 1-phosphate (S1P) signaling have become a successful or promising target for multiple sclerosis or cerebral ischemia. Animal-based proof-of-concept validation for the latter is particularly through the neuroprotective efficacy of FTY720, a non-selective S1P receptor modulator, presumably via activation of S1P1. In spite of a clear link between S1P signaling and cerebral ischemia, it remains unknown whether the role of S1P1 is pathogenic or neuroprotective...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28342971/a-novel-dual-glp-1-gip-receptor-agonist-alleviates-cognitive-decline-by-re-sensitizing-insulin-signaling-in-the-alzheimer-icv-stz-rat-model
#7
Lijuan Shi, Zhihua Zhang, Lin Li, Christian Hölscher
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, accompanied by memory loss and cognitive impairments, and there is no effective treatment for it at present. Since type 2 diabetes (T2DM) has been identified as a risk factor for AD, the incretins glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP), promising antidiabetic agents for the treatment of type 2 diabetes, have been tested in models of neurodegenerative disease including AD and achieved good results...
March 22, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28342781/modulation-of-neuroinflammation-the-role-and-therapeutic-potential-of-transient-receptor-potential-vanilloid-1-in-neuro-immune-axis
#8
REVIEW
Wei-Lin Kong, Yuan-Yuan Peng, Bi-Wen Peng
Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved...
March 22, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28342444/acid-ceramidase-deficiency-in-mice-results-in-a-broad-range-of-central-nervous-system-abnormalities
#9
Jakub Sikora, Shaalee Dworski, E Ellen Jones, Mustafa A Kamani, Matthew C Micsenyi, Tomo Sawada, Pauline Le Faouder, Justine Bertrand-Michel, Aude Dupuy, Christopher K Dunn, Ingrid Cong Yang Xuan, Josefina Casas, Gemma Fabrias, David R Hampson, Thierry Levade, Richard R Drake, Jeffrey A Medin, Steven U Walkley
Farber disease is a rare autosomal recessive disorder caused by acid ceramidase deficiency that usually presents as early-onset progressive visceral and neurologic disease. To understand the neurologic abnormality, we investigated behavioral, biochemical, and cellular abnormalities in the central nervous system of Asah1(P361R/P361R) mice, which serve as a model of Farber disease. Behaviorally, the mutant mice had reduced voluntary locomotion and exploration, increased thigmotaxis, abnormal spectra of basic behavioral activities, impaired muscle grip strength, and defects in motor coordination...
April 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28342179/common-polymorphisms-of-cx3cr1-gene-modify-als-outcome-a-population-based-study
#10
Andrea Calvo, Cristina Moglia, Antonio Canosa, Stefania Cammarosano, Antonio Ilardi, Davide Bertuzzo, Bryan J Traynor, Maura Brunetti, Marco Barberis, Gabriele Mora, Federico Casale, Adriano Chiò
INTRODUCTION: In the brain the CX3CR1 gene is only expressed by microglia where it acts as a key mediator of the neuron-microglia interactions. We assessed whether the two common polymorphisms of the CX3CR1 gene (V249I and T280M) modify amyotrophic lateral sclerosis (ALS) phenotype. METHODS: The study included 755 ALS patients diagnosed in Piemonte between 2007 and 2012 and 369 age- and gender-matched controls, all genotyped using the same chips. RESULTS: Neither of the variants were associated with an increased risk of ALS...
March 25, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28341636/relief-from-neuropathic-pain-by-blocking-of-the-platelet-activating-factor-pain-loop
#11
Hideo Shindou, Seiji Shiraishi, Suzumi M Tokuoka, Yoshikazu Takahashi, Takeshi Harayama, Takaya Abe, Kana Bando, Kanako Miyano, Yoshihiro Kita, Yasuhito Uezono, Takao Shimizu
Neuropathic pain resulting from peripheral neuronal damage is largely resistant to treatment with currently available analgesic drugs. Recently, ATP, lysophosphatidic acid, and platelet-activating factor (PAF) have been reported to play important inductive roles in neuropathic pain. In the present study, we found that pain-like behaviors resulting from partial sciatic nerve ligation (PSL) were largely attenuated by deficiency of lysophosphatidylcholine acyltransferase (LPCAT)2, which is one of the PAF biosynthetic enzymes...
March 24, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28341583/a-story-of-birth-and-death-insights-into-the-formation-and-dynamics-of-the-microglial-population
#12
REVIEW
Katharine Askew, Diego Gomez-Nicola
Microglia are the main resident immunocompetent cells of the brain with key roles in brain development, homeostasis and function. Here we briefly review our current knowledge of the homeostatic mechanisms regulating the composition and turnover of the microglial population under physiological conditions from development to ageing. A greater understanding of these mechanisms may inform understanding of how dysregulation of microglial dynamics could contribute to the pathogenesis and/or progression of neurological disorders...
March 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28341582/sex-differences-in-microglial-phagocytosis-in-the-neonatal-hippocampus
#13
Lars H Nelson, Spencer Warden, Kathryn M Lenz
Microglia regulate brain development through many processes, such as promoting neurogenesis, supporting cell survival, and phagocytizing progenitor, newly-born, and dying cells. Many of these same developmental processes show robust sex differences, yet very few studies have assessed sex differences in microglia function during development. Hormonally-induced sexual differentiation of the brain occurs during the perinatal period, thus we examined sex differences in microglial morphology, phagocytosis, and proliferation in the hippocampus during the early postnatal period...
March 21, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28340598/myelin-specific-multiple-sclerosis-antibodies-cause-complement-dependent-oligodendrocyte-loss-and-demyelination
#14
Yiting Liu, Katherine S Given, Danielle E Harlow, Adeline M Matschulat, Wendy B Macklin, Jeffrey L Bennett, Gregory P Owens
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF. Among these were a subset of myelin-specific MS rAbs. We examined their immunoreactivity to mouse organotypic cerebellar slices by live binding and evaluated tissue injury in the presence and absence of human complement...
March 24, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28340583/inflammatory-signature-of-cerebellar-neurodegeneration-during-neonatal-hyperbilirubinemia-in-ugt1-mouse-model
#15
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
#16
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
#17
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/28339077/paeoniflorin-attenuates-the-neuroinflammatory-response-in-a-rat-model-of-chronic-constriction-injury
#18
Jianyu Zhou, Jingxia Wang, Wei Li, Chenglong Wang, Li Wu, Jianjun Zhang
Neuropathic pain remains the most frequent cause of suffering and disability worldwide. Paeoniflorin (PF), a water‑soluble monoterpene glycoside extracted from the roots of Paeonia lactiflora Pall, has a wide range of pharmacological functions. Although the neuroprotective effect of PF has been reported in animal models of neuropathology, no systematic investigation has reported on the analgesic properties of PF in neuropathic pain. The aim of the present study was to investigate whether PF can alleviate neuropathic pain and to examine its possible mechanism...
March 24, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28338530/pharmacologic-characterizations-of-a-p2x7-receptor-specific-radioligand-11c-gsk1482160-for-neuroinflammatory-response
#19
Junbin Han, Hui Liu, Chunling Liu, Hongjun Jin, Joel S Perlmutter, Terrance M Egan, Zhude Tu
OBJECTIVE: The P2X7 receptor (P2X7R) is a key regulatory element in the neuroinflammatory cascade that provides a promising target for imaging neuroinflammation. GSK1482160, a P2X7R modulator with nanomolar binding affinity and high selectivity, has been successfully radiolabeled and utilized for imaging P2X7 levels in a mouse model of lipopolysaccharide-induced systemic inflammation. In the current study, we further characterized its binding profile and determined whether [C]GSK1482160 can detect changes in P2X7R expression in a rodent model of multiple sclerosis...
March 23, 2017: Nuclear Medicine Communications
https://www.readbyqxmd.com/read/28338241/neuroprotective-effects-of-loganin-on-mptp-induced-parkinson-s-disease-mice-neurochemistry-glial-reaction-and-autophagy-studies
#20
Yi-Da Xu, Chun Cui, Meng-Fei Sun, Ying-Li Zhu, Min Chu, Yun-Wei Shi, Stanley Li Lin, Xu-Sheng Yang, Yan-Qin Shen
Parkinson's disease (PD) is a progressive neurodegenerative disease, involving resting tremor and bradykinesia, for which no recognized therapies or drugs are available to halt or slow progression. In recent years, natural botanic products have been considered relatively safe, with limited side effects, and are expected to become an important source for clinical mediation of PD in the future. Our study focuses on the ability of loganin, a compound derived from fruits of cornus, to mediate neuroprotection in a mouse model of PD...
March 24, 2017: Journal of Cellular Biochemistry
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