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Sample records for neuroinflammation markers adhesion

  1. Dose-dependent changes in neuroinflammatory and arachidonic acid cascade markers with synaptic marker loss in rat lipopolysaccharide infusion model of neuroinflammation

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    Kellom Matthew

    2012-05-01

    Full Text Available Abstract Background Neuroinflammation, caused by six days of intracerebroventricular infusion of bacterial lipopolysaccharide (LPS, stimulates rat brain arachidonic acid (AA metabolism. The molecular changes associated with increased AA metabolism are not clear. We examined effects of a six-day infusion of a low-dose (0.5 ng/h and a high-dose (250 ng/h of LPS on neuroinflammatory, AA cascade, and pre- and post-synaptic markers in rat brain. We used artificial cerebrospinal fluid-infused brains as controls. Results Infusion of low- or high-dose LPS increased brain protein levels of TNFα, and iNOS, without significantly changing GFAP. High-dose LPS infusion upregulated brain protein and mRNA levels of AA cascade markers (cytosolic cPLA2-IVA, secretory sPLA2-V, cyclooxygenase-2 and 5-lipoxygenase, and of transcription factor NF-κB p50 DNA binding activity. Both LPS doses increased cPLA2 and p38 mitogen-activated protein kinase levels, while reducing protein levels of the pre-synaptic marker, synaptophysin. Post-synaptic markers drebrin and PSD95 protein levels were decreased with high- but not low-dose LPS. Conclusions Chronic LPS infusion has differential effects, depending on dose, on inflammatory, AA and synaptic markers in rat brain. Neuroinflammation associated with upregulated brain AA metabolism can lead to synaptic dysfunction.

  2. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease.

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    Levesque, Shannon; Surace, Michael J; McDonald, Jacob; Block, Michelle L

    2011-08-24

    Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE) and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m³) by inhalation over 6 months. DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m³ significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m³ and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m³) in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m³ exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may precede preclinical markers of neurodegenerative disease in the midbrain.

  3. Air pollution & the brain: Subchronic diesel exhaust exposure causes neuroinflammation and elevates early markers of neurodegenerative disease

    Directory of Open Access Journals (Sweden)

    McDonald Jacob

    2011-08-01

    Full Text Available Abstract Background Increasing evidence links diverse forms of air pollution to neuroinflammation and neuropathology in both human and animal models, but the effects of long-term exposures are poorly understood. Objective We explored the central nervous system consequences of subchronic exposure to diesel exhaust (DE and addressed the minimum levels necessary to elicit neuroinflammation and markers of early neuropathology. Methods Male Fischer 344 rats were exposed to DE (992, 311, 100, 35 and 0 μg PM/m3 by inhalation over 6 months. Results DE exposure resulted in elevated levels of TNFα at high concentrations in all regions tested, with the exception of the cerebellum. The midbrain region was the most sensitive, where exposures as low as 100 μg PM/m3 significantly increased brain TNFα levels. However, this sensitivity to DE was not conferred to all markers of neuroinflammation, as the midbrain showed no increase in IL-6 expression at any concentration tested, an increase in IL-1β at only high concentrations, and a decrease in MIP-1α expression, supporting that compensatory mechanisms may occur with subchronic exposure. Aβ42 levels were the highest in the frontal lobe of mice exposed to 992 μg PM/m3 and tau [pS199] levels were elevated at the higher DE concentrations (992 and 311 μg PM/m3 in both the temporal lobe and frontal lobe, indicating that proteins linked to preclinical Alzheimer's disease were affected. α Synuclein levels were elevated in the midbrain in response to the 992 μg PM/m3 exposure, supporting that air pollution may be associated with early Parkinson's disease-like pathology. Conclusions Together, the data support that the midbrain may be more sensitive to the neuroinflammatory effects of subchronic air pollution exposure. However, the DE-induced elevation of proteins associated with neurodegenerative diseases was limited to only the higher exposures, suggesting that air pollution-induced neuroinflammation may

  4. Molecular markers of cell adhesion in ameloblastomas. An update

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    González-González, Rogelio; Molina-Frechero, Nelly; Damian-Matsumura, Pablo

    2014-01-01

    Ameloblastoma is the most common odontogenic tumor of epithelial origin, and though it is of a benign nature, it frequently infiltrates the bone, has a high rate of recurrence and could potentially become malignant. Cellular adhesion potentially plays an important role in the manifestation of these characteristics and in the tumor biology of ameloblastomas. Losses of cell-cell and extracellular matrix adhesion and cohesion are among the first events that occur in the invasion and growth of tumors of epithelial origin. The present review includes a description of the molecules that are involved in cell adhesion as reported for various types of ameloblastomas and discusses the possible roles of these molecules in the biological behaviors of this odontogenic tumor. Knowledge of the complex mechanisms in which these molecules play a role is critical for the research and discovery of future therapeutic targets. Key words:Ameloblastoma, cellular adhesion, molecular markers, cell-cell adhesion, extracellular matrix-cell adhesion. PMID:23986011

  5. Epithelial cell adhesion molecule - More than a carcinoma marker and adhesion molecule

    NARCIS (Netherlands)

    Trzpis, Monika; McLaughlin, Pamela M. J.; de Leij, Lou M. F. H.; Harmsen, Martin C.

    The epithetial cell adhesion molecule (EpCAM, CD326) is a glycoprotein of similar to 40 kd that was originally identified as a marker for carcinoma, attributable to its high expression on rapidly proliferating tumors of epithelial origin. Normal epithelia express EpCAM at a variable but generally

  6. Nilotinib and bosutinib modulate pre-plaque alterations of blood immune markers and neuro-inflammation in Alzheimer's disease models.

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    Lonskaya, I; Hebron, M L; Selby, S T; Turner, R S; Moussa, C E-H

    2015-09-24

    Alzheimer's disease (AD) brains exhibit plaques and tangles in association with inflammation. The non-receptor tyrosine kinase Abl is linked to neuro-inflammation in AD. Abl inhibition by nilotinib or bosutinib facilitates amyloid clearance and may decrease inflammation. Transgenic mice that express Dutch, Iowa and Swedish APP mutations (TgAPP) and display progressive Aβ plaque deposition were treated with tyrosine kinase inhibitors (TKIs) to determine pre-plaque effects on systemic and CNS inflammation using milliplex® ELISA. Plaque Aβ was detected at 4months in TgAPP and pre-plaque intracellular Aβ accumulation (2.5months) was associated with changes of cytokines and chemokines prior to detection of glial changes. Plaque formation correlated with increased levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1α, IL-1β) and markers of immunosuppressive and adaptive immunity, including, IL-4, IL-10, IL-2, IL-3, Vascular Endothelial Growth Factor (VEGF) and IFN-γ. An inverse relationship of chemokines was observed as CCL2 and CCL5 were lower than WT mice at 2months and significantly increased after plaque appearance, while soluble CX3CL1 decreased. A change in glial profile was only robustly detected at 6months in Tg-APP mice and TKIs reduced astrocyte and dendritic cell number with no effects on microglia, suggesting alteration of brain immunity. Nilotinib decreased blood and brain cytokines and chemokines and increased CX3CL1. Bosutinib increased brain and blood IL-10 and CX3CL1, suggesting a protective role for soluble CX3CL1. Taken together these data suggest that TKIs regulate systemic and CNS immunity and may be useful treatments in early AD through dual effects on amyloid clearance and immune modulation. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures

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    Shin, Kwangsoo; Choi, Jin Woo; Ko, Giho; Baik, Seungmin; Kim, Dokyoon; Park, Ok Kyu; Lee, Kyoungbun; Cho, Hye Rim; Han, Sang Ihn; Lee, Soo Hong; Lee, Dong Jun; Lee, Nohyun; Kim, Hyo-Cheol; Hyeon, Taeghwan

    2017-07-01

    Tissue adhesives have emerged as an alternative to sutures and staples for wound closure and reconnection of injured tissues after surgery or trauma. Owing to their convenience and effectiveness, these adhesives have received growing attention particularly in minimally invasive procedures. For safe and accurate applications, tissue adhesives should be detectable via clinical imaging modalities and be highly biocompatible for intracorporeal procedures. However, few adhesives meet all these requirements. Herein, we show that biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) exhibit not only high contrast effects for real-time imaging but also strong adhesive properties. Furthermore, the biocompatible TSNs cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (that is, a mixture of cyanoacrylate and Lipiodol). Because of their multifunctional imaging and adhesive property, the TSNs are successfully applied as a hemostatic adhesive for minimally invasive procedures and as an immobilized marker for image-guided procedures.

  8. Epithelial Cell Adhesion Molecule: More than a Carcinoma Marker and Adhesion Molecule

    National Research Council Canada - National Science Library

    Trzpis, Monika; McLaughlin, Pamela M.J; de Leij, Lou M.F.H; Harmsen, Martin C

    2007-01-01

    From the Department of Pathology and Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands The epithelial cell adhesion molecule (EpCAM, CD326...

  9. A new x-ray adhesive system with embedded nanoparticulate silver markers for dental applications

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    Bessudnova, Nadezda O.; Bilenko, David I.; Venig, Sergey B.; Atkin, Vsevolod S.; Zacharevich, Andrey M.

    2013-02-01

    In the present study a new adhesive system with embedded PVP-stabilized nano-particulate silver markers has been designed. Nanosized silver was used as a radio-opaque contrast material in SEM examination of adhesive system in dentine. It was studied the impact of nano-particulate silver fillers on rheological properties of adhesive system and its penetration in dentine volume. A SEM comparative evaluation of resin replicas produced using adhesive system with embedded silver nanoparticles and that without ones was carried out. It was shown that embedding of silver nanoparticles into adhesive system did not make its penetration worse. It was established that embedding of nanosized silver changed adhesive system morphology. The methodology that allows visualizing interfaces and intermediate layers between dentine, adhesive system and restorative material using silver nano-particulate markers was developed and approved. Silver nanoparticles were used to compare the objective depth of penetration of adhesive systems of different generations in root dentine with differently oriented dentinal tubules, bonding resin delivery and gravity.

  10. New serum markers for small-cell lung cancer. II. The neural cell adhesion molecule, NCAM

    DEFF Research Database (Denmark)

    Vangsted, A; Drivsholm, L; Andersen, E

    1994-01-01

    The neural cell adhesion molecule (NCAM) was recently suggested as a marker for small-cell lung cancer (SCLC). Immunohistochemical analysis demonstrated the presence of the NCAM in 78% of SCLC patients and in 25% of patients with other cancer forms. NCAM was proposed to be the most sensitive marker...... for SCLC, and it may also be an important prognostic marker for SCLC. We used a competitive ELISA to analyze the concentrations of NCAM in sera from 96 SCLC patients, 16 patients with non-SCLC, 4 patients with other cancer forms, and 16 healthy controls. All sera were collected at the time of diagnosis...... serum marker, FucGM1.(ABSTRACT TRUNCATED AT 250 WORDS)...

  11. Neuroinflammation, neurodegeneration, and depression.

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    Hurley, Laura L; Tizabi, Yousef

    2013-02-01

    Neurodegeneration and depression are two common co-morbid conditions, particularly within the aging population. Research has linked neuroinflammation as a major contributing factor to both of these diseases. The key to neuroinflammation effects on neurodegeneration and depression appears to lie within the dysregulation of the control and release of pro- and anti-inflammatory cytokines. This can come from an internal or external insult to the system, or from changes in the individual due to aging that culminate in immune dysregulation. The need to reduce neuroinflammation has led to extensive research into neuroprotectants. We discuss the efficacy found with nicotine, alcohol, resveratrol, curcumin, and ketamine. Our main focus will be on what research tells us about the connections between neuroinflammation, neurodegeneration, and depression, and the hope that neuroprotectants research gives people suffering from neurodegeneration and depression stemming from neuroinflammation. We will conclude by making suggestions for future research in this area.

  12. Adhesions

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    Adhesions are bands of scar-like tissue. Normally, internal tissues and organs have slippery surfaces so they can shift easily as the body moves. Adhesions cause tissues and organs to stick together. They ...

  13. Neuroinflammation in bipolar disorders

    Directory of Open Access Journals (Sweden)

    Georgios D Kotzalidis

    2015-01-01

    Full Text Available Recent literature based on peripheral immunity findings speculated that neuroinflammation, with its connection to microglial activation, is linked to bipolar disorder. The endorsement of the neuroinflammatory hypotheses of bipolar disorder requires the demonstration of causality, which requires longitudinal studies. We aimed to review the evidence for neuroinflammation as a pathogenic mechanism of the bipolar disorder. We carried out a hyper inclusive PubMed search using all appropriate neuroinflammation-related terms and crossed them with bipolar disorder-related terms. The search produced 310 articles and the number rose to 350 after adding articles from other search engines and reference lists. Twenty papers were included that appropriately tackled the issue of the presence (but not of its pathophysiological role of neuroinflammation in bipolar disorder. Of these, 15 were postmortem and 5 were carried out in living humans. Most articles were consistent with the presence of neuroinflammation in bipolar disorder, but factors such as treatment may mask it. All studies were cross-sectional, preventing causality to be inferred. Thus, no inference can be currently made about the role of neuroinflammation in bipolar disorder, but a link is likely. The issue remains little investigated, despite an excess of reviews on this topic.

  14. Neuroinflammation in Lewy body dementia.

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    Surendranathan, Ajenthan; Rowe, James B; O'Brien, John T

    2015-12-01

    Neuroinflammation is increasingly recognized as a key factor in the pathogenesis of neurodegenerative conditions. However, it remains unclear whether it has a protective or damaging role. Studies of Alzheimer's disease and Parkinson's disease have provided much of the evidence for inflammatory pathology in neurodegeneration. Here we review the evidence for inflammation in dementia with Lewy bodies and Parkinson's disease dementia. Neuroinflammation has been confirmed in vivo using PET imaging, with microglial activation seen in Parkinson's disease dementia and recently in dementia with Lewy bodies. In Parkinson's disease and Parkinson's disease dementia, microglial activation suggests a chronic inflammatory process, although there is also evidence of its association with cognitive ability and neuronal function. Alpha-synuclein in various conformations has also been linked to activation of microglia, with a broad range of components of the innate and adaptive immune systems associated with this interaction. Evidence of neuroinflammation in Lewy body dementia is further supported by pathological and biomarker studies. Genetic and epidemiological studies support a role for inflammation in Parkinson's disease, but have yet to provide the same for Lewy body dementia. This review highlights the need to identify whether the nature and extent of microglial activation in Lewy body dementia can be linked to structural change, progression of domain specific cognitive symptoms and peripheral inflammation as a marker of central microglial pathology. Answers to these questions will enable the evaluation of immunotherapies as potential therapeutic options for prevention or treatment of dementia with Lewy bodies and Parkinson's disease dementia. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Cell adhesion molecules and hyaluronic acid as markers of inflammation, fibrosis and response to antiviral therapy in chronic hepatitis C patients

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    Esther Granot

    2001-01-01

    Full Text Available Objective: Cell adhesion molecules (intracellular adhesion molecule-1 (ICAM-1, vascular cell adhesion molecule-1 (VCAM-1 and hyaluronic acid, markers of inflammation and fibrosis were monitored in hepatitis C patients to determine whether changes in plasma levels, during antiviral treatment, can predict long-term response to therapy.

  16. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

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    Schachner Melitta

    2011-05-01

    Full Text Available Abstract Background L1 cell adhesion molecule (CD171 is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Methods Using a sensitive enzyme-linked immunosorbent assay (ELISA, soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Results Median levels of soluble L1 were significantly higher (p p Conclusion These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.

  17. Nutrient-sensing mechanisms in hypothalamic cell models: neuropeptide regulation and neuroinflammation in male- and female-derived cell lines

    National Research Council Canada - National Science Library

    Loganathan, Neruja; Belsham, Denise D

    2016-01-01

    .... Because obesity often results in central neuroinflammation, we describe markers that could be used to study differences between male and female models, both the whole organism and also at the cellular level...

  18. Soluble adhesion molecules as markers for sepsis and the potential pathophysiological discrepancy in neonates, children and adults

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    2014-01-01

    Sepsis is a severe and life-threatening systemic inflammatory response to infection that affects all populations and age groups. The pathophysiology of sepsis is associated with aberrant interaction between leukocytes and the vascular endothelium. As inflammation progresses, the adhesion molecules that mediate these interactions become shed from cell surfaces and accumulate in the blood as soluble isoforms that are being explored as potential prognostic disease biomarkers. We critically review the studies that have tested the predictive value of soluble adhesion molecules in sepsis pathophysiology with emphasis on age, as well as the underlying mechanisms and potential roles for inflammatory shedding. Five soluble adhesion molecules are associated with sepsis, specifically, E-selectin, L-selectin and P-selectin, intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. While increased levels of these soluble adhesion molecules generally correlate well with the presence of sepsis, their degree of elevation is still poorly predictive of sepsis severity scores, outcome and mortality. Separate analyses of neonates, children and adults demonstrate significant age-dependent discrepancies in both basal and septic levels of circulating soluble adhesion molecules. Additionally, a range of both clinical and experimental studies suggests protective roles for adhesion molecule shedding that raise important questions about whether these should positively or negatively correlate with mortality. In conclusion, while predictive properties of soluble adhesion molecules have been researched intensively, their levels are still poorly predictive of sepsis outcome and mortality. We propose two novel directions for improving clinical utility of soluble adhesion molecules: the combined simultaneous analysis of levels of adhesion molecules and their sheddases; and taking age-related discrepancies into account. Further attention to these issues may provide better

  19. Regional Sensitivity to Neuroinflammation: In Vivo and In Vitro Studies

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    Liraz-Zaltsman, S.; Biegon, A.; Liraz-Zaltsman, S.; Alexandrovich, A.G.; Trembovler, V.; Fishbein, I.; Yaka, R.; Shohami, E.; Biegon, A.

    2010-11-23

    Neuroinflammation is involved in several acute-onset neuropathologies such as meningitis, encephalitis, stroke, and traumatic brain injury as well as in neurodegenerative diseases. All of these patholologies are associated with cognitive deficits. Using a model of pure neuroinflammation (intracisternal injection of endotoxin in mice), we tested the hypothesis that brain regions involved in cognition are the most vulnerable to inflammatory insults, and this vulnerability is an inherent property of neocortical neurons. Mice (n = 10/group) injected with endotoxin (LPS) or saline in the cisterna magna underwent neurobehavioral and cognitive testing followed by quantitative autoradiographic assessment of regional neuroinflammation with [3H]PK11195, an established marker of microgliosis. In parallel, cocultures of cortical and striatal neurons taken from embryonic day 19 rat embryos or postnatal day 1 mice expressing green fluorescent protein were exposed for 24 h to the proinflammatory cytokine TNFalpha, glutamate, or a combination of the two agents. LPS-treated mice exhibited significant deficits in memory and significant increases in specific PK11195 binding in cortical and hippocampal regions, but not in striatum. Cultured neurons of cortical origin showed significantly lower survival rate relative to striatal neurons in response to TNFalpha, glutamate, or a combination of the two agents. Furthermore, TNFalpha exerted neuroprotective rather than neurotoxic effects in the striatal but not in the cortical neurons. These results suggest that the cortex is inherently more sensitive than the striatum to the deleterious effects of neuroinflammation, and may offer an explanation for the preponderance of cognitive deficits in neuropathologies with a neuroinflammatory component.

  20. Evaluation of C-Reactive Protein, Endothelin-1, Adhesion Molecule(s, and Lipids as Inflammatory Markers in Type 2 Diabetes Mellitus Patients

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    Hala El-Mesallamy

    2007-01-01

    Full Text Available This study compared lipids, the product of lipid peroxidation malondialdehyde (MDA, the acute phase reactant high sensitive C-reactive protein (hsCRP, endothelin-1 (ET-1, P-selectin, intercellular adhesion molecule-1 (ICAM-1, and vascular cell adhesion molecule-1 (VCAM-1 between healthy controls, subjects with ischemic heart disease (IHD and type 2 diabetes mellitus (DM subjects who did not perform coronary artery bypass graft (CABG surgery as well as type 2 DM subjects who performed CABG. HbA1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1, and VCAM-1 levels were significantly higher in the diabetic groups than in either healthy controls or IHD subjects. In the diabetic groups, there was a negative association among hsCRP and HDL-C. ET-1, ICAM-1 levels and TAG were positively correlated, as do the association between P-selectin, VCAM-1 and HbA1c%. Also a positive relation was found among hsCRP levels and ICAM-1, as well as MDA and ET-1. P-selectin and ICAM-1 were significantly positively correlated. This study indicates that increased level of oxidative stress marker, proinflammatory markers and their downstream effectors adhesion molecules occurs in type 2 DM.

  1. Neuroinflammation in glaucoma: A new opportunity.

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    Williams, Pete A; Marsh-Armstrong, Nick; Howell, Gareth R

    2017-04-01

    Mounting evidence suggests neuroinflammation is a key process in glaucoma, yet the precise roles are not known. Understanding these complex processes, which may also be a key in other common neurodegenerations such as Alzheimer's disease, will lead to targeted therapeutics for a disease that affects as many as 80 million people worldwide. Here, we define neuroinflammation as any immune-relevant response by a variety of cell types including astrocytes, microglia, and peripherally derived cells occurring in the optic nerve head and/or retina. In this review article, we first discuss clinical evidence for neuroinflammation in glaucoma and define neuroinflammation in glaucoma. We then review the inflammatory pathways that have been associated with glaucoma. Finally, we set out key research directions that we believe will greatly advance our understanding of the role of neuroinflammation in glaucoma. This review arose from a discussion of neuroinflammation in glaucoma at the 2015 meeting of The Lasker/IRRF Initiative for Innovation in Vision Science. This manuscript sets out to summarize one of these sessions; "Inflammation and Glaucomatous Neurodegeneration", as well as to review the current state of the literature surrounding neuroinflammation in glaucoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Soluble intercellular adhesion molecule-1 and E-selectin as markers of disease activity and endothelial activation in juvenile idiopathic arthritis.

    Science.gov (United States)

    Bloom, Bradley J; Nelson, Sarah M; Eisenberg, Daniel; Alario, Anthony J

    2005-02-01

    To determine whether soluble forms of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and E-selectin correlate with clinical measures or other markers of endothelial activation in children with juvenile idiopathic arthritis (JIA) over time. A total of 28 children with JIA were studied every 3 months over 2 years. At each interval, serum was tested for soluble (s)ICAM-1 and sE-selectin, plasma for fibrin d-dimer and von Willebrand factor (vWF), and the following clinical variables were recorded: erythrocyte sedimentation rate (ESR), physician and parent global assessments, swollen and limited joint counts, and functional assessment by Childhood Health Assessment Questionnaire. Concentrations of the adhesion molecules were also determined once in 30 age matched healthy children. Among all JIA subtypes, baseline sICAM-1 was elevated compared to controls; sE-selectin was higher in patients with systemic disease compared to other subtypes and controls. sE-selectin correlated with ESR, but there were no other correlations between concentrations of either adhesion molecule or any other clinical variables or vWF antigen. sICAM-1 was higher in those with elevated compared to normal d-dimer. There were no differences between mean sICAM-1 and sE-selectin before or during disease flare or improvement periods, except for an increase in sICAM-1 with flares in patients with systemic disease. sICAM-1 is elevated in children with active JIA. sE-selectin is only elevated in children with active systemic disease. Although some relationships were found between the adhesion molecules and other variables, they did not correlate with most variables, and did not parallel the disease course. Thus, we cannot recommend the routine use of these molecules as clinical biomarkers of disease activity. This study confirms that endothelial activation is key to the pathogenesis of JIA, especially in the systemic subtype.

  3. Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes.

    Science.gov (United States)

    Tremblay, André J; Lamarche, Benoît; Deacon, Carolyn F; Weisnagel, S John; Couture, Patrick

    2014-09-01

    Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized. The objective of the present study was to examine the effects of treatment with sitagliptin on the plasma levels of various markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m²) were recruited into this double-blind, cross-over study using sitagliptin (100mg/d) or placebo, each for a 6-week period, including a 4-week washout period between the two phases. Blood samples were taken at the end of each phase of treatment. Compared with placebo, treatment with sitagliptin significantly reduced the plasma levels of C-reactive protein (CRP) (44.9%, P=0.006), interleukin (IL)-6 (24.7%, P=0.04), IL-18 (7.3%, P=0.004), secreted phospholipase-A₂ (sPLA₂) (12.9%, P=0.04), soluble intercellular adhesion molecule-1 (5.3%, P=0.002), and E-selectin (5.9%, P=0.005). A significant inverse correlation was found between changes in glucagon-like peptide-1 (GLP-1) and changes in CRP levels (r=0.41, P=0.01) following sitagliptin therapy. Sitagliptin therapy had more pronounced effects in subjects with higher levels of inflammatory markers and cell adhesion molecules compared with subjects with lower levels. Treatment with sitagliptin for 6 weeks reduced plasma markers of low-grade inflammation and cell adhesion molecules, most likely by increasing plasma GLP-1 levels and improving glucose-insulin homeostasis. These beneficial effects

  4. Activated leukocyte cell adhesion molecule and prognosis in acute ischemic stroke

    DEFF Research Database (Denmark)

    Smedbakken, Linda; Jensen, Jesper K; Hallén, Jonas

    2011-01-01

    Biomarkers predicting mortality and functional outcome in stroke may be clinically helpful in identification of patients likely to benefit from intervention. Activated leukocyte cell adhesion molecule (ALCAM) is upregulated during neuroinflammation; we investigated whether ALCAM concentrations ar...

  5. Markers of inflammation and cellular adhesion molecules in relation to insulin resistance in nondiabetic elderly: the Rotterdam study

    NARCIS (Netherlands)

    A.E. Hak (Liesbeth); H.A.P. Pols (Huib); C.D. Stehouwer (Coen); J. Meijer (John); A.J. Kiliaan (Amanda); M.M.B. Breteler (Monique); J.C.M. Witteman (Jacqueline); A. Hofman (Albert)

    2001-01-01

    textabstractInsulin resistance, which is highly prevalent in the elderly, is suggested to be accompanied by an increased acute phase response. Until now, it is unclear whether cellular adhesion molecules are involved in the clustering of insulin resistance. In the present study, we

  6. Neurotransmitters and microglial-mediated neuroinflammation.

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    Lee, Moonhee

    2013-02-01

    Reciprocal interactions between cells caused by release of soluble factors are essential for brain function. So far, little attention has been paid to interactions between neurons and glia. However, in the last few decades, studies regarding such interactions have given us some important clues about possible mechanisms underlying degenerative processes in neurological diseases such as Alzheimer's disease and Parkinson's disease. Activated microglia and markers of inflammatory reactions have been consistently found in the post-mortem brains of diseased patients. But it has not been clearly understood how microglia respond to neurotransmitters released from neurons during disease progression. The main purpose of this review is to summarize studies performed on neurotransmitter receptor expression in microglia, and the effects of their activation on microglial-mediated neuroinflammation. A possible mechanism underlying transmitter-mediated modulation of microglial response is also suggested. Microglia express receptors for neurotransmitters such as ATP, adenosine, glutamate, GABA, acetylcholine, dopamine and adrenaline. Activation of GABA, cholinergic and adrenergic receptors suppresses microglial responses, whereas activation of ATP or adenosine receptors activates them. This latter effect may be due primarily to activation of a Ca(2+)-signaling pathway which, in turn, results in activation of MAP kinases and NFkB proteins with the release of proinflammatory factors. However, glutamate and dopamine are both pro- and anti-inflammatory depending on the receptor subtypes expressed in microglia. More detailed studies on downstream receptor-signaling cascades are needed to understand the roles of neurotransmitters in controlling neuron-microglia interactions during inflammatory processes in disease progression. Such knowledge may suggest new methods of treatment.

  7. Peripheral surgical wounding and age-dependent neuroinflammation in mice.

    Directory of Open Access Journals (Sweden)

    Zhipeng Xu

    Full Text Available Post-operative cognitive dysfunction is associated with morbidity and mortality. However, its neuropathogenesis remains largely to be determined. Neuroinflammation and accumulation of β-amyloid (Aβ have been reported to contribute to cognitive dysfunction in humans and cognitive impairment in animals. Our recent studies have established a pre-clinical model in mice, and have found that the peripheral surgical wounding without the influence of general anesthesia induces an age-dependent Aβ accumulation and cognitive impairment in mice. We therefore set out to assess the effects of peripheral surgical wounding, in the absence of general anesthesia, on neuroinflammation in mice with different ages. Abdominal surgery under local anesthesia was established in 9 and 18 month-old mice. The levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, Iba1 positive cells (the marker of microglia activation, CD33, and cognitive function in mice were determined. The peripheral surgical wounding increased the levels of TNF-α, IL-6, and Iba1 positive cells in the hippocampus of both 9 and 18 month-old mice, and age potentiated these effects. The peripheral surgical wounding increased the levels of CD33 in the hippocampus of 18, but not 9, month-old mice. Finally, anti-inflammatory drug ibuprofen ameliorated the peripheral surgical wounding-induced cognitive impairment in 18 month-old mice. These data suggested that the peripheral surgical wounding could induce an age-dependent neuroinflammation and elevation of CD33 levels in the hippocampus of mice, which could lead to cognitive impairment in aged mice. Pending further studies, anti-inflammatory therapies may reduce the risk of postoperative cognitive dysfunction in elderly patients.

  8. The Cox-2 Inhibitor Meloxicam Ameliorates Neuroinflammation and Depressive Behavior in Adult Mice after Splenectomy.

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    Haile, Michael; Boutajangout, Allal; Chung, Kevin; Chan, Jeffrey; Stolper, Tanya; Vincent, Nemahun; Batchan, Marc; D'Urso, John; Lin, Yan; Kline, Richard; Yaghmoor, Faris; Jahfal, Saad; Kamal, Robel; Aljohani, Waleed; Blanck, Thomas; Bekker, Alex; Wisniewski, Thomas

    2016-01-01

    Peripheral surgical trauma may incite neuroinflammation that leads to neuronal dysfunction associated with both depression and cognitive deficits. In a previous study, we found that adult mice developed neuroinflammation and short-term working memory dysfunction in a delayed, transient manner after splenectomy that was ameliorated by the cyclooxygenase-2 inhibitor meloxicam. We tested the hypothesis that splenectomy in mice would also cause anhedonia, the diminished response to pleasure or rewarding stimuli that is a hallmark of depression, and that treatment with meloxicam would be ameliorative. After Institutional Animal Care and Use Committee approval, Swiss-Webster mice underwent sucrose preference training before being randomized into groups on day 0, when they had either splenectomy and anesthesia or anesthesia alone. Within each group, half were randomized to receive intraperitoneal saline at 24 hours, while the other half received intraperitoneal meloxicam at 24 hours. Sucrose preference ratios were determined on days 1, 5, 9, and 14. Additional mice were randomized into groups for brain histochemistry. Specimens were stained for glial fibrillary acidic protein (GFAP), a marker of astrocytes, and CD45, a protein tyrosine phosphatase that identifies microglial activation. On day 5, mice receiving splenectomy and saline demonstrated diminished sucrose preference, which was not seen in mice receiving splenectomy and meloxicam. Semiquantitative analysis of histological slides taken from splenectomized mice treated with meloxicam revealed reduced microglial-based neuroinflammation and reactive astrocytosis compared to mice receiving saline. Splenectomy in mice is associated with neuroinflammation and anhedonia, as evidenced by reactive microgliosis, astrocytosis, and behavioral changes. Postsurgical treatment with meloxicam attenuates both neuroinflammation and anhedonia. These findings suggest that cyclooxygenase-2-dependent mechanisms may play a role in the

  9. Relevance of Neuroinflammation and Encephalitis in Autism

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    Janet eKern

    2016-01-01

    Full Text Available In recent years, many studies indicate that children with an autism spectrum disorder (ASD diagnosis have brain pathology suggestive of ongoing neuroinflammation or encephalitis in different regions of their brains. Evidence of neuroinflammation or encephalitis in ASD includes: microglial and astrocytic activation, a unique and elevated proinflammatory profile of cytokines, and aberrant expression of nuclear factor kappa-light-chain-enhancer of activated B cells. A conservative estimate based on the research suggests that at least 69% of individuals with an ASD diagnosis have microglial activation or neuroinflammation. Encephalitis, which is defined as inflammation of the brain, is medical diagnosis code G04.90 in the International Classification of Disease, 10th revision; however, children with an ASD diagnosis are not generally assessed for a possible medical diagnosis of encephalitis. This is unfortunate because if a child with ASD has neuroinflammation, then treating the underlying brain inflammation could lead to improved outcomes. The purpose of this review of the literature is to examine the evidence of neuroinflammation/encephalitis in those with an ASD diagnosis and to address how a medical diagnosis of encephalitis, when appropriate, could benefit these children by driving more immediate and targeted treatments.

  10. Dinamic changes of pro-inflammatory cytokines, adhesion molecules and lymphocytes activation markers as early indicators of diseases severity in patients with Dengue

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    Silvana Vielma

    2014-09-01

    Full Text Available Several immunopathogenic mechanisms have been proposed to explain the massive increase of vascular permeability observed in the severe forms of infection by Dengue Virus (DENV. Our aim was to determine the kinetic changes of inflammatory mediators (IL-8, TNF- α, soluble early lymphocyte activation markers (sIL-2R, sTNF-Rp75 and soluble fractions of cell adhesion molecules (sICAM-1 and sVCAM-1 as indicators for early recognition of disease severity in patients with laboratory-confirmed dengue. Twenty patients classified as Dengue±Warning Signs (D±WS and thirty patients with Severe Dengue (SD were included in the study. Serums of apparently healthy individuals were included as controls. Compared with normal subjects, D±WS cases did not show significant differences in the levels of IL-8 or TNF-α during the acute nor in the critical stages of the disease; however, in D±WS cases levels of sICAM-1 and sVCAM-1 were higher than controls during both phases; in contrast, significant increase of sTNF-p75 and sIL2R levels were observed during the critical phase of the disease. Compared with both dengue patients and controls, patients with SD showed significant rise in the levels of IL-8 and TNF-α during the critical phase of the disease and a significant increase in adhesion molecules were detected in both phases, but the highest levels of sVCAM-1 and sIL-2R were observed only during the acute stage of the disease. In conclusion, sIL-2R and sVCAM-1, as early markers of lymphocyte and endothelial activation, would serves as indicators of severity during the acute phase of dengue infection.

  11. Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration

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    Cheng, Shanshan; Hou, Jinxing; Zhang, Chen; Xu, Congyu; Wang, Long; Zou, Xiaoxia; Yu, Huahong; Shi, Yun; Yin, Zhenyu; Chen, Guiquan

    2015-01-01

    Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis. PMID:26000566

  12. EGFR transactivation contributes to neuroinflammation in Streptococcus suis meningitis.

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    Yang, Xiao-Pei; Fu, Ji-Yang; Yang, Rui-Cheng; Liu, Wen-Tong; Zhang, Tao; Yang, Bo; Miao, Ling; Dou, Bei-Bei; Tan, Chen; Chen, Huan-Chun; Wang, Xiang-Ru

    2016-10-19

    Streptococcus suis serotype 2 (SS2) is an important zoonotic bacterial pathogen in both humans and animals, which can cause high morbidity and mortality. Meningitis is one of the major clinical manifestations of SS2 infection. However, the specific process of SS2 meningitis and its molecular mechanisms remain unclear. Epidermal growth factor receptor (EGFR) has been reported to initiate transduction of intracellular signals and regulate host inflammatory responses. Whether and how EGFR contributes to the development of S. suis meningitis are currently unknown. The tyrosine phosphorylation of cellular proteins, the transactivation of EGFR, as well as its dimerization, and the associated signal transduction pathways were investigated by immunoprecipitation and western blotting. Real-time quantitative PCR was used to investigate the transcriptional level of the ErbB family members, EGFR-related ligands, cytokines, and chemokines. The secretion of cytokines and chemokines in the serum and brain were detected by Q-Plex™ Chemiluminescent ELISA. We found an important role of EGFR in SS2 strain SC19-induced meningitis. SC19 increasingly adhered to human brain microvascular endothelial cells (hBMEC) and caused inflammatory lesions in the brain tissues, with significant induction and secretion of proinflammatory cytokines and chemokines in the serum and brains. SC19 infection of hBMEC induced tyrosine phosphorylation of cellular EGFR in a ligand-dependent manner involving the EGF-like ligand HB-EGF, amphiregulin (AREG), and epiregulin (EREG) and led to heterodimerization of EGFR/ErbB3. The EGFR transactivation did not participate in SS2 strain SC19 adhesion of hBMEC, as well as in bacterial colonization in vivo. However, its transactivation contributed to the bacterial-induced neuroinflammation, via triggering the MAPK-ERK1/2 and NF-κB signaling pathways in hBMEC that promote the production of proinflammatory cytokines and chemokines. We investigated for the first time

  13. Mast cells in neuroinflammation and brain disorders

    NARCIS (Netherlands)

    Hendriksen, Erik; van Bergeijk, Doris; Oosting, Ronald S; Redegeld, Frank A

    2017-01-01

    It is well recognized that neuroinflammation is involved in the pathogenesis of various neurodegenerative diseases. Microglia and astrocytes are major pathogenic components within this process and known to respond to proinflammatory mediators released from immune cells such as mast cells. Mast cells

  14. Activated leukocyte cell adhesion molecule (ALCAM) is a marker of recurrence and promotes cell migration, invasion, and metastasis in early-stage endometrioid endometrial cancer.

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    Devis, Laura; Moiola, Cristian P; Masia, Nuria; Martinez-Garcia, Elena; Santacana, Maria; Stirbat, Tomita Vasilica; Brochard-Wyart, Françoise; García, Ángel; Alameda, Francesc; Cabrera, Silvia; Palacios, Jose; Moreno-Bueno, Gema; Abal, Miguel; Thomas, William; Dufour, Sylvie; Matias-Guiu, Xavier; Santamaria, Anna; Reventos, Jaume; Gil-Moreno, Antonio; Colas, Eva

    2017-03-01

    Endometrial cancer is the most common gynaecological cancer in western countries, being the most common subtype of endometrioid tumours. Most patients are diagnosed at an early stage and present an excellent prognosis. However, a number of those continue to suffer recurrence, without means of identification by risk classification systems. Thus, finding a reliable marker to predict recurrence becomes an important unmet clinical issue. ALCAM is a cell-cell adhesion molecule and member of the immunoglobulin superfamily that has been associated with the genesis of many cancers. Here, we first determined the value of ALCAM as a marker of recurrence in endometrioid endometrial cancer by conducting a retrospective multicentre study of 174 primary tumours. In early-stage patients (N = 134), recurrence-free survival was poorer in patients with ALCAM-positive compared to ALCAM-negative tumours (HR 4.237; 95% CI 1.01-17.76). This difference was more significant in patients with early-stage moderately-poorly differentiated tumours (HR 9.259; 95% CI 2.12-53.47). In multivariate analysis, ALCAM positivity was an independent prognostic factor in early-stage disease (HR 6.027; 95% CI 1.41-25.74). Then we demonstrated in vitro a role for ALCAM in cell migration and invasion by using a loss-of-function model in two endometrial cancer cell lines. ALCAM depletion resulted in a reduced primary tumour size and reduced metastatic local spread in an orthotopic murine model. Gene expression analysis of ALCAM-depleted cell lines pointed to motility, invasiveness, cellular assembly, and organization as the most deregulated functions. Finally, we assessed some of the downstream effector genes that are involved in ALCAM-mediated cell migration; specifically FLNB, TXNRD1, and LAMC2 were validated at the mRNA and protein level. In conclusion, our results highlight the potential of ALCAM as a recurrent biomarker in early-stage endometrioid endometrial cancer and point to ALCAM as an important

  15. Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains.

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    Adzovic, Linda; Lynn, Ashley E; D'Angelo, Heather M; Crockett, Alexis M; Kaercher, Roxanne M; Royer, Sarah E; Hopp, Sarah C; Wenk, Gary L

    2015-04-02

    The role of insulin in the brain is still not completely understood. In the periphery, insulin can decrease inflammation induced by lipopolysaccharide (LPS); however, whether insulin can reduce inflammation within the brain is unknown. Experiments administrating intranasal insulin to young and aged adults have shown that insulin improves memory. In our animal model of chronic neuroinflammation, we administered insulin and/or LPS directly into the brain via the fourth ventricle for 4 weeks in young rats; we then analyzed their spatial memory and neuroinflammatory response. Additionally, we administered insulin or artificial cerebral spinal fluid (aCSF), in the same manner, to aged rats and then analyzed their spatial memory and neuroinflammatory response. Response to chronic neuroinflammation in young rats was analyzed in the presence or absence of insulin supplementation. Here, we show for the first time that insulin infused (i.c.v.) to young rats significantly attenuated the effects of LPS by decreasing the expression of neuroinflammatory markers in the hippocampus and by improving performance in the Morris water pool task. In young rats, insulin infusion alone significantly improved their performance as compared to all other groups. Unexpectedly, in aged rats, the responsiveness to insulin was completely absent, that is, spatial memory was still impaired suggesting that an age-dependent insulin resistance may contribute to the cognitive impairment observed in neurodegenerative diseases. Our data suggest a novel therapeutic effect of insulin on neuroinflammation in the young but not the aged brain.

  16. Striatal neuroinflammation promotes Parkinsonism in rats.

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    Dong-Young Choi

    Full Text Available Sporadic Parkinson's disease (PD is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors contribute to dopaminergic neuronal death in PD.In this study, we analyzed the relationship among inducible nitric oxide synthase (iNOS-derived NO, mitochondrial dysfunction and dopaminergic neurodegeneration to examine the possibility that microglial neuroinflammation may induce dopaminergic neuronal loss in the substantia nigra. Unilateral injection of lipopolysaccharide (LPS into the striatum of rat was followed by immunocytochemical, histological, neurochemical and biochemical analyses. In addition, behavioral assessments including cylinder test and amphetamine-induced rotational behavior test were employed to validate ipsilateral damage to the dopamine nigrostriatal pathway. LPS injection caused progressive degeneration of the dopamine nigrostriatal system, which was accompanied by motor impairments including asymmetric usage of forelimbs and amphetamine-induced turning behavior in animals. Interestingly, some of the remaining nigral dopaminergic neurons had intracytoplasmic accumulation of alpha-synuclein and ubiquitin. Furthermore, defect in the mitochondrial respiratory chain, and extensive S-nitrosylation/nitration of mitochondrial complex I were detected prior to the dopaminergic neuronal loss. The mitochondrial injury was prevented by treatment with L-N(6-(l-iminoethyl-lysine, an iNOS inhibitor, suggesting that iNOS-derived NO is associated with the mitochondrial impairment.These results implicate neuroinflammation-induced S-nitrosylation/nitration of mitochondrial complex I in mitochondrial malfunction and subsequent degeneration of the nigral dopamine

  17. Emerging roles of protein kinases in microglia-mediated neuroinflammation.

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    Lee, Sun-Hwa; Suk, Kyoungho

    2017-12-15

    Neuroinflammation is mediated by resident central nervous system glia, neurons, peripherally derived immune cells, blood-brain barrier, and inflammatory mediators secreted from these cells. Neuroinflammation has been implicated in stroke and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Protein kinases have been one of the most exploited therapeutic targets in the current pharmacological research, especially in studies on cancer and inflammation. To date, 32 small-molecule protein kinase inhibitors have been approved by the United States Food and Drug Administration for the treatment of cancer and inflammation. However, there is no drug effectively targeting neuroinflammation and/or neurodegenerative diseases. Recent studies have advanced several protein kinases as important drug targets in neuroinflammation and/or neurodegenerative diseases. Here, we review emerging protein kinases potentially involved in neuroinflammation and subsequent neurodegenerative diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Minocycline attenuates lipopolysaccharide (LPS-induced neuroinflammation, sickness behavior, and anhedonia

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    Bailey Michael T

    2008-05-01

    Full Text Available Abstract Background Activation of the peripheral innate immune system stimulates the secretion of CNS cytokines that modulate the behavioral symptoms of sickness. Excessive production of cytokines by microglia, however, may cause long-lasting behavioral and cognitive complications. The purpose of this study was to determine if minocycline, an anti-inflammatory agent and purported microglial inhibitor, attenuates lipopolysaccharide (LPS-induced neuroinflammation, sickness behavior, and anhedonia. Methods In the first set of experiments the effect of minocycline pretreatment on LPS-induced microglia activation was assessed in BV-2 microglia cell cultures. In the second study, adult (3–6 m BALB/c mice received an intraperitoneal (i.p. injection of vehicle or minocycline (50 mg/kg for three consecutive days. On the third day, mice were also injected (i.p. with saline or Escherichia coli LPS (0.33 mg/kg and behavior (i.e., sickness and anhedonia and markers of neuroinflammation (i.e., microglia activation and inflammatory cytokines were determined. In the final study, adult and aged BALB/c mice were treated with the same minocycline and LPS injection regimen and markers of neuroinflammation were determined. All data were analyzed using Statistical Analysis Systems General Linear Model procedures and were subjected to one-, two-, or three-way ANOVA to determine significant main effects and interactions. Results Minocycline blocked LPS-stimulated inflammatory cytokine secretion in the BV-2 microglia-derived cell line and reduced LPS-induced Toll-like-receptor-2 (TLR2 surface expression on brain microglia. Moreover, minocycline facilitated the recovery from sickness behavior (i.e., anorexia, weight loss, and social withdrawal and prevented anhedonia in adult mice challenged with LPS. Furthermore, the minocycline associated recovery from LPS-induced sickness behavior was paralleled by reduced mRNA levels of Interleukin (IL-1β, IL-6, and indoleamine 2

  19. Progranulin in frontotemporal lobar degeneration and neuroinflammation

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    Hutton Michael L

    2007-02-01

    Full Text Available Abstract Progranulin (PGRN is a pleiotropic protein that has gained the attention of the neuroscience community with recent discoveries of mutations in the gene for PGRN that cause frontotemporal lobar degeneration (FTLD. Pathogenic mutations in PGRN result in null alleles, and the disease is likely the result of haploinsufficiency. Little is known about the normal function of PGRN in the central nervous system apart from a role in brain development. It is expressed by microglia and neurons. In the periphery, PGRN is involved in wound repair and inflammation. High PGRN expression has been associated with more aggressive growth of various tumors. The properties of full length PGRN are distinct from those of proteolytically derived peptides, referred to as granulins (GRNs. While PGRN has trophic properties, GRNs are more akin to inflammatory mediators such as cytokines. Loss of the neurotrophic properties of PGRN may play a role in selective neuronal degeneration in FTLD, but neuroinflammation may also be important. Gene expression studies suggest that PGRN is up-regulated in a variety of neuroinflammatory conditions, and increased PGRN expression by microglia may play a pivotal role in the response to brain injury, neuroinflammation and neurodegeneration.

  20. Neuroinflammation and neurological alterations in chronic liver diseases

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    Carmina Montoliu

    2015-01-01

    Full Text Available Several million people with chronic liver diseases (cirrhosis, hepatitis show neurological alterations, named hepatic encephalopathy (HE with cognitive and motor alterations that impair quality of life and reduces life span. Inflammation acts synergistically with hyperammonemia to induce cognitive and motor alterations in patients with chronic liver disease and minimal hepatic encephalopathy (MHE. Previous studies in animal models have suggested that neuroinflammation is a major player in HE. This would also be the case in patients with liver cirrhosis or hepatitis C with HE. Rats with MHE show microglial activation and neuroinflammation that is associated with cognitive impairment and hypokinesia. The anti-inflammatory drug ibuprofen reduces microglial activation and neuroinflammation and restores cognitive and motor functions in rats with MHE. Chronic hyperammonemia per se induces neuroinflammation. Both peripheral inflammation and hyperammonemia would contribute to neuroinflammation in chronic liver failure. Therefore, neuroinflammation may be a key therapeutic target to improve the cognitive and motor alterations in MHE and overt HE. Identifying new targets to reduce neuroinflammation in MHE without inducing secondary effects would serve to develop new therapeutic tools to reverse the cognitive and motor alterations in patients with HE associated with chronic liver diseases.

  1. Calcium dysregulation via L-type voltage-dependent calcium channels and ryanodine receptors underlies memory deficits and synaptic dysfunction during chronic neuroinflammation.

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    Hopp, Sarah C; D'Angelo, Heather M; Royer, Sarah E; Kaercher, Roxanne M; Crockett, Alexis M; Adzovic, Linda; Wenk, Gary L

    2015-03-25

    Chronic neuroinflammation and calcium (Ca(+2)) dysregulation are both components of Alzheimer's disease. Prolonged neuroinflammation produces elevation of pro-inflammatory cytokines and reactive oxygen species which can alter neuronal Ca(+2) homeostasis via L-type voltage-dependent Ca(+2) channels (L-VDCCs) and ryanodine receptors (RyRs). Chronic neuroinflammation also leads to deficits in spatial memory, which may be related to Ca(+2) dysregulation. The studies herein use an in vivo model of chronic neuroinflammation: rats were infused intraventricularly with a continuous small dose of lipopolysaccharide (LPS) or artificial cerebrospinal fluid (aCSF) for 28 days. The rats were treated with the L-VDCC antagonist nimodipine or the RyR antagonist dantrolene. LPS-infused rats had significant memory deficits in the Morris water maze, and this deficit was ameliorated by treatment with nimodipine. Synaptosomes from LPS-infused rats had increased Ca(+2) uptake, which was reduced by a blockade of L-VDCCs either in vivo or ex vivo. Taken together, these data indicate that Ca(+2) dysregulation during chronic neuroinflammation is partially dependent on increases in L-VDCC function. However, blockade of the RyRs also slightly improved spatial memory of the LPS-infused rats, demonstrating that other Ca(+2) channels are dysregulated during chronic neuroinflammation. Ca(+2)-dependent immediate early gene expression was reduced in LPS-infused rats treated with dantrolene or nimodipine, indicating normalized synaptic function that may underlie improvements in spatial memory. Pro-inflammatory markers are also reduced in LPS-infused rats treated with either drug. Overall, these data suggest that Ca(+2) dysregulation via L-VDCCs and RyRs play a crucial role in memory deficits resulting from chronic neuroinflammation.

  2. Neuro-inflammation, blood-brain barrier, seizures and autism

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    Theoharides Theoharis C

    2011-11-01

    Full Text Available Abstract Many children with Autism Spectrum Diseases (ASD present with seizure activity, but the pathogenesis is not understood. Recent evidence indicates that neuro-inflammation could contribute to seizures. We hypothesize that brain mast cell activation due to allergic, environmental and/or stress triggers could lead to focal disruption of the blood-brain barrier and neuro-inflammation, thus contributing to the development of seizures. Treating neuro-inflammation may be useful when anti-seizure medications are ineffective.

  3. Neuroinflammation, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice.

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    Toufik Taib

    Full Text Available Traumatic brain injury (TBI results in white matter injury (WMI that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i neuroinflammation, (ii WMI and (iii behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact. (i For neuroinflammation, IL-1b protein as well as microglial phenotypes, by gene expression for 12 microglial activation markers on isolated CD11b+ cells from brains, were studied after TBI. IL-1b protein was increased at 6 hours and 1 day. TBI induced a mixed population of microglial phenotypes with both pro-inflammatory, anti-inflammatory and immunomodulatory markers from 6 hours to 3 days post-injury. At 7 days, microglial activation was completely resolved. (ii Three myelin proteins were assessed after TBI on ipsi- and contralateral corpus callosum, as this structure is enriched in white matter. TBI led to an increase in 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a marker of immature and mature oligodendrocyte, at 2 days post-injury; a bilateral demyelination, evaluated by myelin basic protein, from 7 days to 3 months post-injury; and an increase in myelin oligodendrocyte glycoprotein at 6 hours and 3 days post-injury. Transmission electron microscopy study revealed various myelin sheath abnormalities within the corpus callosum at 3 months post-TBI. (iii TBI led to sensorimotor deficits at 3 days post-TBI, and late cognitive flexibility disorder evidenced by the reversal learning task of the Barnes maze 3 months after injury. These data give an overall invaluable overview of time course of neuroinflammation that could be involved in demyelination and late cognitive disorder over a time-scale of 3 months in a model

  4. Neuroinflammation, myelin and behavior: Temporal patterns following mild traumatic brain injury in mice

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    Taib, Toufik; Leconte, Claire; Van Steenwinckel, Juliette; Cho, Angelo H.; Palmier, Bruno; Torsello, Egle; Lai Kuen, Rene; Onyeomah, Somfieme; Ecomard, Karine; Benedetto, Chiara; Coqueran, Bérard; Novak, Anne-Catherine; Deou, Edwige; Plotkine, Michel; Gressens, Pierre; Marchand-Leroux, Catherine

    2017-01-01

    Traumatic brain injury (TBI) results in white matter injury (WMI) that is associated with neurological deficits. Neuroinflammation originating from microglial activation may participate in WMI and associated disorders. To date, there is little information on the time courses of these events after mild TBI. Therefore we investigated (i) neuroinflammation, (ii) WMI and (iii) behavioral disorders between 6 hours and 3 months after mild TBI. For that purpose, we used experimental mild TBI in mice induced by a controlled cortical impact. (i) For neuroinflammation, IL-1b protein as well as microglial phenotypes, by gene expression for 12 microglial activation markers on isolated CD11b+ cells from brains, were studied after TBI. IL-1b protein was increased at 6 hours and 1 day. TBI induced a mixed population of microglial phenotypes with both pro-inflammatory, anti-inflammatory and immunomodulatory markers from 6 hours to 3 days post-injury. At 7 days, microglial activation was completely resolved. (ii) Three myelin proteins were assessed after TBI on ipsi- and contralateral corpus callosum, as this structure is enriched in white matter. TBI led to an increase in 2',3'-cyclic-nucleotide 3'-phosphodiesterase, a marker of immature and mature oligodendrocyte, at 2 days post-injury; a bilateral demyelination, evaluated by myelin basic protein, from 7 days to 3 months post-injury; and an increase in myelin oligodendrocyte glycoprotein at 6 hours and 3 days post-injury. Transmission electron microscopy study revealed various myelin sheath abnormalities within the corpus callosum at 3 months post-TBI. (iii) TBI led to sensorimotor deficits at 3 days post-TBI, and late cognitive flexibility disorder evidenced by the reversal learning task of the Barnes maze 3 months after injury. These data give an overall invaluable overview of time course of neuroinflammation that could be involved in demyelination and late cognitive disorder over a time-scale of 3 months in a model of mild TBI

  5. Chronic exercise ameliorates the neuroinflammation in mice carrying NSE/htau23

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    Leem, Yea-Hyun, E-mail: leemyy@empas.com [Exercise Biochemistry Laboratory, Korea National Sport University, Seoul 138-763 (Korea, Republic of); Lee, Young-Ik, E-mail: lee0ik@hanmail.net [Department of Oriental Sports Medicine, Daegu Hanny University, Daegu 712-715 (Korea, Republic of); Son, Hee-Jeong, E-mail: son1106@paran.com [Exercise Physiology Laboratory, Korea National Sport University, Seoul 138-763 (Korea, Republic of); Lee, Sang-Ho, E-mail: run2025@hanmail.net [Department of Sports for All, Kangnam University, Yongin 446-702 (Korea, Republic of)

    2011-03-18

    Research highlights: {yields} The progress of neurodegeration are directly linked to the neuroinflammatory response. {yields} We investigate whether exercise improves the neuroinflammation using T{sub g}-NSE/htau23 mice. {yields} This provides insights that exercise may beneficial effects on the neuroinflammatory disorders. -- Abstract: The objective of the present study was to investigate whether chronic endurance exercise attenuates the neuroinflammation in the brain of mice with NSE/htau23. In this study, the tau-transgenic (Tg) mouse, Tg-NSE/htau23, which over expresses human Tau23 in its brain, was subjected to chronic exercise for 3 months, from 16 months of age. The brains of Tg mice exhibited increased immunoreactivity and active morphological changes in GFAP (astrocyte marker) and MAC-1 (microglia marker) expression in an age-dependent manner. To identify the effects of chronic exercise on gliosis, the exercised Tg mice groups were treadmill run at a speed of 12 m/min (intermediate exercise group) or 19 m/min (high exercise group) for 1 h/day and 5 days/week during the 3 month period. The neuroinflammatory response characterized by activated astroglia and microglia was significantly repressed in the exercised Tg mice in an exercise intensity-dependent manner. In parallel, chronic exercise in Tg mice reduced the increased expression of TNF-{alpha}, IL-6, IL-1{beta}, COX-2, and iNOS. Consistently with these changes, the levels of phospho-p38 and phospho-ERK were markedly downregulated in the brain of Tg mice after exercise. In addition, nuclear NF-{kappa}B activity was profoundly reduced after chronic exercise in an exercise intensity-dependent manner. These findings suggest that chronic endurance exercise may alleviate neuroinflammation in the Tau pathology of Alzheimer's disease.

  6. Magnesium Sulfate Provides Neuroprotection in Eclampsia-Like Seizure Model by Ameliorating Neuroinflammation and Brain Edema.

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    Li, Xiaolan; Han, Xinjia; Yang, Jinying; Bao, Junjie; Di, Xiaodan; Zhang, Guozheng; Liu, Huishu

    2016-11-22

    Eclampsia is a hypertensive disorder of pregnancy that is defined by the new onset of grand mal seizures on the basis of preeclampsia and a leading cause of maternal and fetal mortality worldwide. Presently, magnesium sulfate (MgSO4) is the most effective treatment, but the mechanism by which MgSO4 prevents eclampsia has yet to be fully elucidated. We previously showed that systemic inflammation decreases the seizure threshold in a rat eclampsia-like model, and MgSO4 treatment can decrease systemic inflammation. Here, we hypothesized that MgSO4 plays a neuroprotective role in eclampsia by reducing neuroinflammation and brain edema. Pregnant Sprague-Dawley rats were given an intraperitoneal injection of pentylenetetrazol following a tail vein injection of lipopolysaccharide to establish the eclampsia-like seizure model. Seizure activity was assessed by behavioral testing. Neuronal loss in the hippocampal CA1 region (CA1) was detected by Nissl staining. Cerebrospinal fluid levels of S100-B and ferritin, indicators of neuroinflammation, were detected by enzyme-linked immunosorbent assay, and ionized calcium binder adapter molecule 1 (Iba-1, a marker for microglia) and glial fibrillary acid protein (GFAP, a marker for astrocytes) expression in the CA1 area was determined by immunofluorescence staining. Brain edema was measured. Our results revealed that MgSO4 effectively attenuated seizure severity and CA1 neuronal loss. In addition, MgSO4 significantly reduced cerebrospinal fluid levels of S100-B and ferritin, Iba-1 and GFAP activation in the CA1 area, and brain edema. Our results indicate that MgSO4 plays a neuroprotective role against eclampsia-like seizure by reducing neuroinflammation and brain edema.

  7. Diesel exhaust activates and primes microglia: air pollution, neuroinflammation, and regulation of dopaminergic neurotoxicity.

    Science.gov (United States)

    Levesque, Shannon; Taetzsch, Thomas; Lull, Melinda E; Kodavanti, Urmila; Stadler, Krisztian; Wagner, Alison; Johnson, Jo Anne; Duke, Laura; Kodavanti, Prasada; Surace, Michael J; Block, Michelle L

    2011-08-01

    Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood. Here, we sought to address the brain-region-specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity. Rats were exposed to DE (2.0, 0.5, and 0 mg/m3) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron-glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms. Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuroinflammation. Analysis by brain region revealed that DE increased TNFα (tumor necrosis factor-α), IL-1β, IL-6, MIP-1α (macrophage inflammatory protein-1α) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNFα at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 μg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFα release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 μg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity. Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity.

  8. Robust spinal neuroinflammation mediates mechanical allodynia in Walker 256 induced bone cancer rats

    Directory of Open Access Journals (Sweden)

    Mao-Ying Qi-Liang

    2012-05-01

    Full Text Available Abstract It has been reported that remarkable and sustained activation of astrocytes and/or microglia occurs in cancer induced pain (CIP, which is different from neuropathic and inflammatory pain. The present study was designed to investigate the role of spinal Toll-like receptor 4 (TLR4 induced glial neuroinflammation in cancer induced pain using a modified rat model of bone cancer. The rat model of CIP consisted of unilateral intra-tibial injection with Walker 256 mammary gland carcinoma. Nine days after Walker 256 inoculation, a robust activation of both astrocytes and microglia in bilateral spinal dorsal horn was observed together with significant bilateral mechanical allodynia. This neuroinflammation was characterized by enhanced immunostaining of both glial fibrillary acidic protein (GFAP, astrocyte marker and OX-42 (microglia marker, and an elevated level of IL-1β, IL-6 and TNF-α mRNA. I.t. administration of fluorocitrate (an inhibitor of glial metabolism, 1 nmol or minocycline (an inhibitor of microglia, 100 μg has significant anti-allodynic effects on day 12 after Walker 256 inoculation. Naloxone (a nonstereoselective TLR4 signaling blocker, 60 μg, i.t. also significantly alleviated mechanical allodynia and simultaneously blocked the increased inflammatory cytokine mRNA. The results suggested that spinal TLR4 might play an important role in the sustained glial activation that critically contributed to the robust and sustained spinal neuroinflammation in CIP. This result could potentially help clinicians and researchers to better understand the mechanism of complicated cancer pain.

  9. How does Diet influence Behavior and Neuroinflammation?

    DEFF Research Database (Denmark)

    Jørgensen, Bettina Merete Pyndt; Hansen, Julie Torpe; Hansen, Axel Jacob Kornerup

    A high number of Non-responders in induced animal models of depression is a problem in research as it results in a high work load and a waste of animals. The aim of this project is to investigate the possible relationship between diet, gut microbiota (GM), low-grade inflammation in the brain......, and behavior in order to generate knowledge enabling researchers to increase the number of responders when inducing these models using environmental modulation. The hypothesis is that a diet-induced change in GM composition can induce a cytokine mediated low-grade neuroinflammation, which is also observed...... in psychiatric diseases such as depression, thereby affecting the behavior. Furthermore the role of Brain Derived Neutrophic Factor (BDNF) in depressive behavior is investigated. 42 male BALB/c mice were divided in to three groups, and fed either a high-fat/low-sugar diet, a high-sugar/low-fat diet or a control...

  10. Mitochondrial dysfunction: A potential link between neuroinflammation and neurodegeneration?

    NARCIS (Netherlands)

    Witte, M.E.; Geurts, J.J.G.; de Vries, H.E.; van der Valk, P.; van Horssen, J.

    2010-01-01

    Dysfunctional mitochondria are thought to play a cardinal role in the pathogenesis of various neurological disorders, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease and stroke. In addition, neuroinflammation is a common denominator of these diseases. Both mitochondrial

  11. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

    NARCIS (Netherlands)

    van Dijk, Gertjan; van Heijningen, Steffen; Reijne, Aaffien C.; Nyakas, Csaba; van der Zee, Eddy A.; Eisel, Ulrich L. M.

    2015-01-01

    Alzheimer's disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid peptide, tau protein hyperphosphorylation, relocalization, and deposition. These mechanisms are propagated by

  12. Emerging targets in neuroinflammation-driven chronic pain

    Science.gov (United States)

    Ji, Ru-Rong; Xu, Zhen-Zhong; Gao, Yong-Jing

    2014-01-01

    Current analgesics predominately modulate pain transduction and transmission in neurons and have limited success in controlling disease progression. Accumulating evidence suggests that neuroinflammation, which is characterized by infiltration of immune cells, activation of glial cells and production of inflammatory mediators in the peripheral and central nervous system, has an important role in the induction and maintenance of chronic pain. This review focuses on emerging targets such as chemokines, proteases and the Wnt pathway that promote spinal cord neuroinflammation and chronic pain. It also highlights the anti-inflammatory and pro-resolution lipid mediators that act on immune cells, glial cells and neurons to resolve neuroinflammation, synaptic plasticity and pain. Targeting excessive neuroinflammation could offer new therapeutic opportunities for chronic pain and related neurological and psychiatric disorders. PMID:24948120

  13. Combinations of ketamine and atropine are neuroprotective and reduce neuroinflammation after a toxic status epilepticus in mice

    Energy Technology Data Exchange (ETDEWEB)

    Dhote, Franck, E-mail: franck.dhote@irba.fr [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Carpentier, Pierre; Barbier, Laure [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Peinnequin, André [Département Effets biologiques des rayonnements, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); Baille, Valérie; Pernot, Fabien; Testylier, Guy; Beaup, Claire; Foquin, Annie [Département de Toxicologie et risques chimiques, Institut de Recherche Biomédicale des armées – Centre de recherches du Service de santé des armées IRBA-CRSSA, 24 avenue des Maquis du Grésivaudan, B.P. 87, 38702 La Tronche cedex (France); and others

    2012-03-01

    Epileptic seizures and status epilepticus (SE) induced by the poisoning with organophosphorus nerve agents (OP), like soman, are accompanied by neuroinflammation whose role in seizure-related brain damage (SRBD) is not clear. Antagonists of the NMDA glutamate ionotropic receptors are currently among the few compounds able to arrest seizures and provide neuroprotection even during refractory status epilepticus (RSE). Racemic ketamine (KET), in combination with atropine sulfate (AS), was previously shown to counteract seizures and SRBD in soman-poisoned guinea-pigs. In a mouse model of severe soman-induced SE, we assessed the potentials of KET/AS combinations as a treatment for SE/RSE-induced SRBD and neuroinflammation. When starting 30 min after soman challenge, a protocol involving six injections of a sub-anesthetic dose of KET (25 mg/kg) was evaluated on body weight loss, brain damage, and neuroinflammation whereas during RSE, anesthetic protocols were considered (KET 100 mg/kg). After confirming that during RSE, KET injection was to be repeated despite some iatrogenic deaths, we used these proof-of-concept protocols to study the changes in mRNA and related protein contents of some inflammatory cytokines, chemokines and adhesion molecules in cortex and hippocampus 48 h post-challenge. In both cases, the KET/AS combinations showed important neuroprotective effects, suppressed neutrophil granulocyte infiltration and partially suppressed glial activation. KET/AS could also reduce the increase in mRNA and related pro-inflammatory proteins provoked by the poisoning. In conclusion, the present study confirms that KET/AS treatment has a strong potential for SE/RSE management following OP poisoning. The mechanisms involved in the reduction of central neuroinflammation remain to be studied. -- Highlights: ► During soman-induced status epilepticus, ketamine-atropine limit brain damage. ► Molecular neuroinflammatory response is strongly decreased. ► Glial activation is

  14. CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation.

    Science.gov (United States)

    Wu, Fengjiao; Zhao, Yawei; Jiao, Tian; Shi, Dongyan; Zhu, Xingxing; Zhang, Mingshun; Shi, Meiqing; Zhou, Hong

    2015-05-21

    Chemokines and chemokine receptors cooperate to promote immune cell recruitment to the central nervous system (CNS). In this study, we investigated the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine model of neuroinflammation. Wild-type (WT), CXCL1(-/-), and CXCR2(-/-) mice each received an intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). Esterase staining and intravital microscopy were performed to examine neutrophil recruitment to the brain. To assess endothelial activation in these mice, the expression of adhesion molecules was measured via quantitative real-time polymerase chain reaction (PCR) and Western blotting. To identify the cellular source of functional CXCR2, chimeric mice were generated by transferring bone marrow cells between the WT and CXCR2(-/-) mice. Expression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1 deficiency blocked neutrophil infiltration and leukocyte recruitment in the cerebral microvessels. In the CXCR2(-/-) and CXCL1(-/-) mice, the cerebral endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was dramatically reduced. Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. Compared with microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro. Astrocyte culture conditioned medium significantly increased the expression of VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner. Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells but not in microglia or astrocytes was increased following tumor necrosis factor-α (TNF-α) stimulation. The intravenous injection of the CXCR2 antagonist SB225002 significantly inhibited endothelial activation and leukocyte recruitment to

  15. Cellular injury and neuroinflammation in children with chronic intractable epilepsy

    Directory of Open Access Journals (Sweden)

    Rosenow Joshua

    2009-12-01

    Full Text Available Abstract Objective To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery. Methods Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6, encephalomalacia (5, Rasmussen's encephalitis (1 or mesial temporal lobe epilepsy (1. Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases. Results Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy. Conclusions Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.

  16. Cellular injury and neuroinflammation in children with chronic intractable epilepsy.

    Science.gov (United States)

    Choi, Jieun; Nordli, Douglas R; Alden, Tord D; DiPatri, Arthur; Laux, Linda; Kelley, Kent; Rosenow, Joshua; Schuele, Stephan U; Rajaram, Veena; Koh, Sookyong

    2009-12-19

    To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery. Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases. Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy. Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.

  17. Intracranial electrode implantation produces regional neuroinflammation and memory deficits in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kuttner-Hirshler, Y.; Biegon, A.; Kuttner-Hirshler, Y.; Polat, U.; Biegon, A.

    2009-12-21

    Deep brain stimulation (DBS) is an established treatment for advanced Parkinson's disease (PD). The procedure entails intracranial implantation of an electrode in a specific brain structure followed by chronic stimulation. Although the beneficial effects of DBS on motor symptoms in PD are well known, it is often accompanied by cognitive impairments, the origin of which is not fully understood. To explore the possible contribution of the surgical procedure itself, we studied the effect of electrode implantation in the subthalamic nucleus (STN) on regional neuroinflammation and memory function in rats implanted bilaterally with stainless steel electrodes. Age-matched sham and intact rats were used as controls. Brains were removed 1 or 8 weeks post-implantation and processed for in vitro autoradiography with [(3)H]PK11195, an established marker of microglial activation. Memory function was assessed by the novel object recognition test (ORT) before surgery and 2 and 8 weeks after surgery. Electrode implantation produced region-dependent changes in ligand binding density in the implanted brains at 1 as well as 8 weeks post-implantation. Cortical regions showed more intense and widespread neuroinflammation than striatal or thalamic structures. Furthermore, implanted animals showed deficits in ORT performance 2 and 8 weeks post-implantation. Thus, electrode implantation resulted in a widespread and persistent neuroinflammation and sustained memory impairment. These results suggest that the insertion and continued presence of electrodes in the brain, even without stimulation, may lead to inflammation-mediated cognitive deficits in susceptible individuals, as observed in patients treated with DBS.

  18. Neuroinflammation in Alzheimer's disease wanes with age.

    Science.gov (United States)

    Hoozemans, Jeroen J M; Rozemuller, Annemieke J M; van Haastert, Elise S; Eikelenboom, Piet; van Gool, Willem A

    2011-12-07

    Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated. In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years). The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1), HLA class II (CR3/43) and glial fibrillary acidic protein (GFAP). By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD. Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease. © 2011 Hoozemans et al; licensee BioMed Central Ltd.

  19. Neuroinflammation in Alzheimer's disease wanes with age

    Directory of Open Access Journals (Sweden)

    Hoozemans Jeroen JM

    2011-12-01

    Full Text Available Abstract Background Inflammation is a prominent feature in Alzheimer's disease (AD. It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated. Methods In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years. The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1, HLA class II (CR3/43 and glial fibrillary acidic protein (GFAP. Results By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD. Conclusion Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.

  20. Adhesive Categories

    DEFF Research Database (Denmark)

    Lack, Stephen; Sobocinski, Pawel

    2003-01-01

    We introduce adhesive categories, which are categories with structure ensuring that pushouts along monomorphisms are well-behaved. Many types of graphical structures used in computer science are shown to be examples of adhesive categories. Double-pushout graph rewriting generalises well...... to rewriting on arbitrary adhesive categories....

  1. Adhesive Categories

    DEFF Research Database (Denmark)

    Lack, Stephen; Sobocinski, Pawel

    2004-01-01

    We introduce adhesive categories, which are categories with structure ensuring that pushouts along monomorphisms are well-behaved. Many types of graphical structures used in computer science are shown to be examples of adhesive categories. Double-pushout graph rewriting generalises well...... to rewriting on arbitrary adhesive categories....

  2. Tetrahydroxystilbene Glucoside Attenuates Neuroinflammation through the Inhibition of Microglia Activation

    Directory of Open Access Journals (Sweden)

    Feng Zhang

    2013-01-01

    Full Text Available Neuroinflammation is closely implicated in the pathogenesis of neurological diseases. The hallmark of neuroinflammation is the microglia activation. Upon activation, microglia are capable of producing various proinflammatory factors and the accumulation of these factors contribute to the neuronal damage. Therefore, inhibition of microglia-mediated neuroinflammation might hold potential therapy for neurological disorders. 2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG, an active component extracted from Polygonum multiflorum, is reported to be beneficial for human health with a great number of pharmacological properties including antioxidant, free radical-scavenging, anti-inflammation, antilipemia, and cardioprotective effects. Recently, TSG-mediated neuroprotective effects have been well demonstrated. However, the neuroprotective actions of TSG on microglia-induced neuroinflammation are not known. In the present study, microglia BV2 cell lines were applied to investigate the anti-neuroinflammatory effects of TSG. Results showed that TSG reduced LPS-induced microglia-derived release of proinflammatory factors such as TNFα, IL-1β, and NO. Moreover, TSG attenuated LPS-induced NADPH oxidase activation and subsequent reactive oxygen species (ROS production. Further studies indicated that TSG inhibited LPS-induced NF-κB signaling pathway activation. Together, TSG exerted neuroprotection against microglia-mediated neuroinflammation, suggesting that TSG might present a promising benefit for neurological disorders treatment.

  3. Aneurysmal Subarachnoid Hemorrhage and Neuroinflammation: A Comprehensive Review

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    Brandon P. Lucke-Wold

    2016-04-01

    Full Text Available Aneurysmal subarachnoid hemorrhage (SAH can lead to devastating outcomes including vasospasm, cognitive decline, and even death. Currently, treatment options are limited for this potentially life threatening injury. Recent evidence suggests that neuroinflammation plays a critical role in injury expansion and brain damage. Red blood cell breakdown products can lead to the release of inflammatory cytokines that trigger vasospasm and tissue injury. Preclinical models have been used successfully to improve understanding about neuroinflammation following aneurysmal rupture. The focus of this review is to provide an overview of how neuroinflammation relates to secondary outcomes such as vasospasm after aneurysmal rupture and to critically discuss pharmaceutical agents that warrant further investigation for the treatment of subarachnoid hemorrhage. We provide a concise overview of the neuroinflammatory pathways that are upregulated following aneurysmal rupture and how these pathways correlate to long-term outcomes. Treatment of aneurysm rupture is limited and few pharmaceutical drugs are available. Through improved understanding of biochemical mechanisms of injury, novel treatment solutions are being developed that target neuroinflammation. In the final sections of this review, we highlight a few of these novel treatment approaches and emphasize why targeting neuroinflammation following aneurysmal subarachnoid hemorrhage may improve patient care. We encourage ongoing research into the pathophysiology of aneurysmal subarachnoid hemorrhage, especially in regards to neuroinflammatory cascades and the translation to randomized clinical trials.

  4. Systemic Immune Activation Leads to Neuroinflammation and Sickness Behavior in Mice

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    Steven Biesmans

    2013-01-01

    Full Text Available Substantial evidence indicates an association between clinical depression and altered immune function. Systemic administration of bacterial lipopolysaccharide (LPS is commonly used to study inflammation-associated behavioral changes in rodents. In these experiments, we tested the hypothesis that peripheral immune activation leads to neuroinflammation and depressive-like behavior in mice. We report that systemic administration of LPS induced astrocyte activation in transgenic GFAP-luc mice and increased immunoreactivity against the microglial marker ionized calcium-binding adapter molecule 1 in the dentate gyrus of wild-type mice. Furthermore, LPS treatment caused a strong but transient increase in cytokine levels in the serum and brain. In addition to studying LPS-induced neuroinflammation, we tested whether sickness could be separated from depressive-like behavior by evaluating LPS-treated mice in a panel of behavioral paradigms. Our behavioral data indicate that systemic LPS administration caused sickness and mild depressive-like behavior. However, due to the overlapping time course and mild effects on depression-related behavior per se, it was not possible to separate sickness from depressive-like behavior in the present rodent model.

  5. Momordica charantia (bitter melon attenuates high-fat diet-associated oxidative stress and neuroinflammation

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    Feher Domonkos

    2011-06-01

    Full Text Available Abstract Background The rising epidemic of obesity is associated with cognitive decline and is considered as one of the major risk factors for neurodegenerative diseases. Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases. Increased metabolic flux to the brain during overnutrition and obesity can orchestrate stress response, blood-brain barrier (BBB disruption, recruitment of inflammatory immune cells from peripheral blood and microglial cells activation leading to neuroinflammation. The lack of an effective treatment for obesity-associated brain dysfunction may have far-reaching public health ramifications, urgently necessitating the identification of appropriate preventive and therapeutic strategies. The objective of our study was to investigate the neuroprotective effects of Momordica charantia (bitter melon on high-fat diet (HFD-associated BBB disruption, stress and neuroinflammatory cytokines. Methods C57BL/6 female mice were fed HFD with and without bitter melon (BM for 16 weeks. BBB disruption was analyzed using Evans blue dye. Phosphate-buffered saline (PBS perfused brains were analyzed for neuroinflammatory markers such as interleukin-22 (IL-22, IL-17R, IL-16, NF-κB1, and glial cells activation markers such as Iba1, CD11b, GFAP and S100β. Additionally, antioxidant enzymes, ER-stress proteins, and stress-resistant transcription factors, sirtuin 1 (Sirt1 and forkhead box class O transcription factor (FoxO were analyzed using microarray, quantitative real-time RT-PCR, western immunoblotting and enzymatic assays. Systemic inflammation was analyzed using cytokine antibody array. Results BM ameliorated HFD-associated changes in BBB permeability as evident by reduced leakage of Evans blue dye. HFD-induced glial cells activation and expression of neuroinflammatory markers such as NF-κB1, IL-16, IL-22 as well as IL-17R were normalized in the brains of mice supplemented with BM

  6. Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism.

    Science.gov (United States)

    Mattsson, Niklas; Bremell, Daniel; Anckarsäter, Rolf; Blennow, Kaj; Anckarsäter, Henrik; Zetterberg, Henrik; Hagberg, Lars

    2010-06-22

    The metabolism of amyloid precursor protein (APP) and beta-amyloid (Abeta) is widely studied in Alzheimer's disease, where Abeta deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB). The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy) and 22 healthy controls. CSF was analysed for the beta-amyloid peptides Abeta38, Abeta40 and Abeta42, and the amyloid precursor protein (APP) isoforms alpha-sAPP and beta-sAPP. CSF total-tau (T-tau), phosphorylated tau (P-tau) and neurofilament protein (NFL) were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers. In the cross-sectional study, LNB patients had lower levels of CSF alpha-sAPP, beta-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF alpha-sAPP, beta-sAPP and P-tau at baseline, which all increased towards normal at follow-up. Amyloid metabolism is altered in LNB. CSF levels of alpha-sAPP, beta-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.

  7. Neuroinflammation in Lyme neuroborreliosis affects amyloid metabolism

    Directory of Open Access Journals (Sweden)

    Anckarsäter Henrik

    2010-06-01

    Full Text Available Abstract Background The metabolism of amyloid precursor protein (APP and β-amyloid (Aβ is widely studied in Alzheimer's disease, where Aβ deposition and plaque development are essential components of the pathogenesis. However, the physiological role of amyloid in the adult nervous system remains largely unknown. We have previously found altered cerebral amyloid metabolism in other neuroinflammatory conditions. To further elucidate this, we investigated amyloid metabolism in patients with Lyme neuroborreliosis (LNB. Methods The first part of the study was a cross-sectional cohort study in 61 patients with acute facial palsy (19 with LNB and 42 with idiopathic facial paresis, Bell's palsy and 22 healthy controls. CSF was analysed for the β-amyloid peptides Aβ38, Aβ40 and Aβ42, and the amyloid precursor protein (APP isoforms α-sAPP and β-sAPP. CSF total-tau (T-tau, phosphorylated tau (P-tau and neurofilament protein (NFL were measured to monitor neural cell damage. The second part of the study was a prospective cohort-study in 26 LNB patients undergoing consecutive lumbar punctures before and after antibiotic treatment to study time-dependent dynamics of the biomarkers. Results In the cross-sectional study, LNB patients had lower levels of CSF α-sAPP, β-sAPP and P-tau, and higher levels of CSF NFL than healthy controls and patients with Bell's palsy. In the prospective study, LNB patients had low levels of CSF α-sAPP, β-sAPP and P-tau at baseline, which all increased towards normal at follow-up. Conclusions Amyloid metabolism is altered in LNB. CSF levels of α-sAPP, β-sAPP and P-tau are decreased in acute infection and increase after treatment. In combination with earlier findings in multiple sclerosis, cerebral SLE and HIV with cerebral engagement, this points to an influence of neuroinflammation on amyloid metabolism.

  8. Neuroinflammation increases GABAergic tone and impairs cognitive and motor function in hyperammonemia by increasing GAT-3 membrane expression. Reversal by sulforaphane by promoting M2 polarization of microglia.

    Science.gov (United States)

    Hernandez-Rabaza, Vicente; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Gonzalez-Usano, Alba; Agusti, Ana; Balzano, Tiziano; Llansola, Marta; Felipo, Vicente

    2016-04-18

    Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive and motor impairment in hepatic encephalopathy (HE). The link between neuroinflammation and GABAergic tone remains unknown. New treatments reducing neuroinflammation and GABAergic tone could improve neurological impairment. The aims were, in hyperammonemic rats, to assess whether: (a) Enhancing endogenous anti-inflammatory mechanisms by sulforaphane treatment reduces neuroinflammation and restores learning and motor coordination. (b) Reduction of neuroinflammation by sulforaphane normalizes extracellular GABA and glutamate-NO-cGMP pathway and identify underlying mechanisms. (c) Identify steps by which hyperammonemia-induced microglial activation impairs cognitive and motor function and how sulforaphane restores them. We analyzed in control and hyperammonemic rats, treated or not with sulforaphane, (a) learning in the Y maze; (b) motor coordination in the beam walking; (c) glutamate-NO-cGMP pathway and extracellular GABA by microdialysis; (d) microglial activation, by analyzing by immunohistochemistry or Western blot markers of pro-inflammatory (M1) (IL-1b, Iba-1) and anti-inflammatory (M2) microglia (Iba1, IL-4, IL-10, Arg1, YM-1); and (e) membrane expression of the GABA transporter GAT-3. Hyperammonemia induces activation of astrocytes and microglia in the cerebellum as assessed by immunohistochemistry. Hyperammonemia-induced neuroinflammation is associated with increased membrane expression of the GABA transporter GAT-3, mainly in activated astrocytes. This is also associated with increased extracellular GABA in the cerebellum and with motor in-coordination and impaired learning ability in the Y maze. Sulforaphane promotes polarization of microglia from the M1 to the M2 phenotype, reducing IL-1b and increasing IL-4, IL-10, Arg1, and YM-1 in the cerebellum. This is associated with astrocytes deactivation and normalization of GAT-3 membrane

  9. Inhibition of neuroinflammation by cinnamon and its main components.

    Science.gov (United States)

    Ho, Su-Chen; Chang, Ku-Shang; Chang, Pei-Wen

    2013-06-15

    Uncontrolled activation of microglia contributes to neuroinflammation, which is highly involved in the development of neurodegenerative diseases. Although cinnamon has neuro-protective properties, its capacity to inhibit neuroinflammation has not been investigated and its active compounds remain unclear. Therefore, the composition of cinnamon extract was analysed by LC-MS and the ability of cinnamon and its main constituents to inhibit neuroinflammation was evaluated using a lipopolysaccharide (LPS)-activated BV2 microglia culture system. In total, 50 μg/mL cinnamon extract decreased significantly the production and expression of nitric oxide (NO), interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in LPS-activated BV2 microglia. Blocking of nuclear factor-κB (NF-κB) activation was the most likely mechanism responsible for inhibition by cinnamon of neuroinflammation. Among the eight tested compounds, cinnamaldehyde had the greatest anti-neuroinflammatory capacity. Experimental results suggest that cinnamon may have a potential therapeutic effect against neurodegenerative diseases and its potent anti-neuroinflammatory capacity was primarily attributed to cinnamaldehyde. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Evaluation of neuroinflammation in X-linked adrenoleukodystrophy.

    Science.gov (United States)

    Kumar, Ajay; Chugani, Harry T; Chakraborty, Pulak; Huq, A H M Mahbubul

    2011-02-01

    We present findings of (11)C-[R]-PK11195 positron emission tomography in a child with X-linked adrenoleukodystrophy. (11)C-[R]-PK11195 is a radioligand with a high and specific affinity for peripheral benzodiazepine receptors, expressed by activated microglia in cases of neuroinflammation, and therefore it is applicable to the in vivo detection of neuroinflammation with positron emission tomography. (11)C-[R]-PK11195 positron emission tomography demonstrated increased tracer binding in the occipital, parietal, and posterior temporal white matter, in the genu of the corpus callosum, the bilateral posterior thalami, most of the posterior limb of the internal capsule, the bilateral cerebral peduncles, and the brainstem, indicating underlying neuroinflammation. The rest of the brain, including the cerebral cortices and cerebellum, exhibited minimal (11)C-[R]-PK11195 binding. Our findings indicate significant neuroinflammation associated with white matter destruction in X-linked adrenoleukodystrophy, which can be visualized in vivo with an (11)C-[R]-PK11195 positron emission tomography scan. (11)C-[R]-PK11195 positron emission tomography may also help evaluate the inflammatory burden and follow-up of the disease evolution. This technique may be particularly useful for evaluating treatment response, which is not easy with other imaging modalities, after white matter is significantly and extensively damaged. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Neuroinflammation - using big data to inform clinical practice.

    Science.gov (United States)

    Dendrou, Calliope A; McVean, Gil; Fugger, Lars

    2016-12-01

    Neuroinflammation is emerging as a central process in many neurological conditions, either as a causative factor or as a secondary response to nervous system insult. Understanding the causes and consequences of neuroinflammation could, therefore, provide insight that is needed to improve therapeutic interventions across many diseases. However, the complexity of the pathways involved necessitates the use of high-throughput approaches to extensively interrogate the process, and appropriate strategies to translate the data generated into clinical benefit. Use of 'big data' aims to generate, integrate and analyse large, heterogeneous datasets to provide in-depth insights into complex processes, and has the potential to unravel the complexities of neuroinflammation. Limitations in data analysis approaches currently prevent the full potential of big data being reached, but some aspects of big data are already yielding results. The implementation of 'omics' analyses in particular is becoming routine practice in biomedical research, and neuroimaging is producing large sets of complex data. In this Review, we evaluate the impact of the drive to collect and analyse big data on our understanding of neuroinflammation in disease. We describe the breadth of big data that are leading to an evolution in our understanding of this field, exemplify how these data are beginning to be of use in a clinical setting, and consider possible future directions.

  12. Cellular Adhesion and Adhesion Molecules

    OpenAIRE

    SELLER, Zerrin

    2014-01-01

    In recent years, cell adhesion and cell adhesion molecules have been shown to be important for many normal biological processes, including embryonic cell migration, immune system functions and wound healing. It has also been shown that they contribute to the pathogenesis of a large number of common human disorders, such as rheumatoid arthritis and tumor cell metastasis in cancer. In this review, the basic mechanisms of cellular adhesion and the structural and functional features of adhes...

  13. Bacterial adhesion

    NARCIS (Netherlands)

    Loosdrecht, van M.C.M.

    1988-01-01

    As mentioned in the introduction of this thesis bacterial adhesion has been studied from a variety of (mostly practice oriented) starting points. This has resulted in a range of widely divergent approaches. In order to elucidate general principles in bacterial adhesion phenomena, we felt it

  14. Denture Adhesives

    Science.gov (United States)

    ... Devices Home Medical Devices Products and Medical Procedures Dental Devices Denture Adhesives Share Tweet Linkedin Pin it More sharing options ... Manufacturers (February 23, 2011) (PDF - 22KB) More in Dental Devices Denture Adhesives Multiple-Use Dental Dispenser Devices Dental Amalgam About ...

  15. Neuroinflammation, Bone Marrow Stem Cells, and Chronic Pain

    Directory of Open Access Journals (Sweden)

    Yul Huh

    2017-08-01

    Full Text Available Current treatments for chronic pain, such as inflammatory pain, neuropathic pain, and cancer pain are insufficient and cause severe side effects. Mounting evidence suggests that neuroinflammation in the peripheral and central nervous system (PNS and CNS plays a pivotal role in the genesis and maintenance of chronic pain. Characteristic features of neuroinflammation in chronic pain conditions include infiltration of immune cells into the PNS [e.g., the sciatic nerve and dorsal root ganglion (DRG], activation of glial cells such as microglia and astrocytes in the CNS (spinal cord and brain, and production and secretion of pro-inflammatory cytokines and chemokines [TNF, interleukin (IL-1β, IL-6, CCL2, and CXCL1]. Recent studies suggest that bone marrow stem cells or bone marrow stromal cells (BMSCs produce powerful analgesic effects in animal models of inflammatory pain, neuropathic pain, and cancer pain. We recently demonstrated that intrathecal injection of BMSCs resulted in a long-term relief of neuropathic pain for several weeks after peripheral nerve injury. Strikingly, this analgesic effect is mediated by the anti-inflammatory cytokine transforming growth factor beta secreted from BMSCs. Additionally, BMSCs exhibit potent modulation of neuroinflammation, by inhibiting monocyte infiltration, glial activation, and cytokine/chemokine production in the DRG and spinal cord. Thus, BMSCs control chronic pain by regulation of neuroinflammation in the PNS and CNS via paracrine signaling. In this review, we discuss the similar results from different laboratories of remarkable anti-nociceptive efficacy of BMSCs in animal and clinical studies. We also discuss the mechanisms by which BMSCs control neuroinflammation and chronic pain and how these cells specifically migrate to damaged tissues.

  16. Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane.

    Science.gov (United States)

    Hernández-Rabaza, Vicente; Cabrera-Pastor, Andrea; Taoro-González, Lucas; Malaguarnera, Michele; Agustí, Ana; Llansola, Marta; Felipo, Vicente

    2016-02-16

    Patients with liver cirrhosis and minimal hepatic encephalopathy (MHE) show mild cognitive impairment and spatial learning dysfunction. Hyperammonemia acts synergistically with inflammation to induce cognitive impairment in MHE. Hyperammonemia-induced neuroinflammation in hippocampus could contribute to spatial learning impairment in MHE. Two main aims of this work were: (1) to assess whether chronic hyperammonemia increases inflammatory factors in the hippocampus and if this is associated with microglia and/or astrocytes activation and (2) to assess whether hyperammonemia-induced neuroinflammation in the hippocampus is associated with altered membrane expression of glutamate and GABA receptors and spatial learning impairment. There are no specific treatments for cognitive alterations in patients with MHE. A third aim was to assess whether treatment with sulforaphane enhances endogenous the anti-inflammatory system, reduces neuroinflammation in the hippocampus of hyperammonemic rats, and restores spatial learning and if normalization of receptor membrane expression is associated with learning improvement. We analyzed the following in control and hyperammonemic rats, treated or not with sulforaphane: (1) microglia and astrocytes activation by immunohistochemistry, (2) markers of pro-inflammatory (M1) (IL-1β, IL-6) and anti-inflammatory (M2) microglia (Arg1, YM-1) by Western blot, (3) membrane expression of GABA, AMPA, and NMDA receptors using the BS3 cross-linker, and (4) spatial learning using the radial maze. The results reported show that hyperammonemia induces astrocytes and microglia activation in the hippocampus, increasing pro-inflammatory cytokines IL-1β and IL-6. This is associated with altered membrane expression of AMPA, NMDA, and GABA receptors which would be responsible for altered neurotransmission and impairment of spatial learning in the radial maze. Treatment with sulforaphane promotes microglia differentiation from pro-inflammatory M1 to anti

  17. Adhesive organ regeneration in Macrostomum lignano.

    Science.gov (United States)

    Lengerer, Birgit; Hennebert, Elise; Flammang, Patrick; Salvenmoser, Willi; Ladurner, Peter

    2016-06-02

    Flatworms possess pluripotent stem cells that can give rise to all cell types, which allows them to restore lost body parts after injury or amputation. This makes flatworms excellent model systems for studying regeneration. In this study, we present the adhesive organs of a marine flatworm as a simple model system for organ regeneration. Macrostomum lignano has approximately 130 adhesive organs at the ventral side of its tail plate. One adhesive organ consists of three interacting cells: one adhesive gland cell, one releasing gland cell, and one modified epidermal cell, called an anchor cell. However, no specific markers for these cell types were available to study the regeneration of adhesive organs. We tested 15 commercially available lectins for their ability to label adhesive organs and found one lectin (peanut agglutinin) to be specific to adhesive gland cells. We visualized the morphology of regenerating adhesive organs using lectin- and antibody staining as well as transmission electron microscopy. Our findings indicate that the two gland cells differentiate earlier than the connected anchor cells. Using EdU/lectin staining of partially amputated adhesive organs, we showed that their regeneration can proceed in two ways. First, adhesive gland cell bodies are able to survive partial amputation and reconnect with newly formed anchor cells. Second, adhesive gland cell bodies are cleared away, and the entire adhesive organ is build anew. Our results provide the first insights into adhesive organ regeneration and describe ten new markers for differentiated cells and tissues in M. lignano. The position of adhesive organ cells within the blastema and their chronological differentiation have been shown for the first time. M. lignano can regenerate adhesive organs de novo but also replace individual anchor cells in an injured organ. Our findings contribute to a better understanding of organogenesis in flatworms and enable further molecular investigations of cell

  18. Development of PET tracers for neuro inflammation imaging in neuro degenerative diseases; Developpement de radiotraceurs de la neuroinflammation pour l'imagerie des pathologies neurodegeneratives

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, F

    2007-10-15

    Inflammatory processes such as micro-glial or endothelial activation are involved in many neuro-degenerative conditions. Neuro-inflammation imaging is considered an attractive tool for fundamental research, diagnosis and therapeutic evaluation in neuro-pathologies. First, an aptamer was selected against a recombinant fragment of the endothelial target VCAM-1, but proved unable to bind the target protein in native conformation, as expressed by a cell line. Second, five radioligands of the peripheral benzodiazepine receptor (PBR), a marker of micro-glial activation, were evaluated in vivo using PET (Positron Emission Tomography) imaging in a rat model of neuro-inflammation, and were compared to [11C]PK11195. Four radiotracers displayed a better contrast than [11C]PK11195. In a competitive field of research, this work demonstrates the efficiency of in vivo screening of radiotracers for fast selection of clinically relevant molecules. (author)

  19. Outdoor Ambient Air Pollution and Neurodegenerative Diseases: the Neuroinflammation Hypothesis.

    Science.gov (United States)

    Jayaraj, Richard L; Rodriguez, Eric A; Wang, Yi; Block, Michelle L

    2017-06-01

    Accumulating research indicates that ambient outdoor air pollution impacts the brain and may affect neurodegenerative diseases, yet the potential underlying mechanisms are poorly understood. The neuroinflammation hypothesis holds that elevation of cytokines and reactive oxygen species in the brain mediates the deleterious effects of urban air pollution on the central nervous system (CNS). Studies in human and animal research document that neuroinflammation occurs in response to several inhaled pollutants. Microglia are a prominent source of cytokines and reactive oxygen species in the brain, implicated in the progressive neuron damage in diverse neurodegenerative diseases, and activated by inhaled components of urban air pollution through both direct and indirect pathways. The MAC1-NOX2 pathway has been identified as a mechanism through which microglia respond to different forms of air pollution, suggesting a potential common deleterious pathway. Multiple direct and indirect pathways in response to air pollution exposure likely interact in concert to exert CNS effects.

  20. Funding free and universal access to Journal of Neuroinflammation.

    Science.gov (United States)

    Mrak, Robert E; Griffin, W Sue T

    2004-10-14

    Journal of Neuroinflammation is an Open Access, online journal published by BioMed Central. Open Access publishing provides instant and universal availability of published work to any potential reader, worldwide, completely free of subscriptions, passwords, and charges. Further, authors retain copyright for their work, facilitating its dissemination. Open Access publishing is made possible by article-processing charges assessed "on the front end" to authors, their institutions, or their funding agencies. Beginning November 1, 2004, the Journal of Neuroinflammation will introduce article-processing charges of around US$525 for accepted articles. This charge will be waived for authors from institutions that are BioMed Central members, and in additional cases for reasons of genuine financial hardship. These article-processing charges pay for an electronic submission process that facilitates efficient and thorough peer review, for publication costs involved in providing the article freely and universally accessible in various formats online, and for the processes required for the article's inclusion in PubMed and its archiving in PubMed Central, e-Depot, Potsdam and INIST. There is no remuneration of any kind provided to the Editors-in-Chief, to any members of the Editorial Board, or to peer reviewers; all of whose work is entirely voluntary. Our article-processing charge is less than charges frequently levied by traditional journals: the Journal of Neuroinflammation does not levy any additional page or color charges on top of this fee, and there are no reprint costs as publication-quality pdf files are provided, free, for distribution in lieu of reprints. Our article-processing charge will enable full, immediate, and continued Open Access for all work published in Journal of Neuroinflammation. The benefits from such Open Access will accrue to readers, through unrestricted access; to authors, through the widest possible dissemination of their work; and to science and

  1. Funding free and universal access to Journal of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Griffin W Sue T

    2004-10-01

    Full Text Available Abstract Journal of Neuroinflammation is an Open Access, online journal published by BioMed Central. Open Access publishing provides instant and universal availability of published work to any potential reader, worldwide, completely free of subscriptions, passwords, and charges. Further, authors retain copyright for their work, facilitating its dissemination. Open Access publishing is made possible by article-processing charges assessed "on the front end" to authors, their institutions, or their funding agencies. Beginning November 1, 2004, the Journal of Neuroinflammation will introduce article-processing charges of around US$525 for accepted articles. This charge will be waived for authors from institutions that are BioMed Central members, and in additional cases for reasons of genuine financial hardship. These article-processing charges pay for an electronic submission process that facilitates efficient and thorough peer review, for publication costs involved in providing the article freely and universally accessible in various formats online, and for the processes required for the article's inclusion in PubMed and its archiving in PubMed Central, e-Depot, Potsdam and INIST. There is no remuneration of any kind provided to the Editors-in-Chief, to any members of the Editorial Board, or to peer reviewers; all of whose work is entirely voluntary. Our article-processing charge is less than charges frequently levied by traditional journals: the Journal of Neuroinflammation does not levy any additional page or color charges on top of this fee, and there are no reprint costs as publication-quality pdf files are provided, free, for distribution in lieu of reprints. Our article-processing charge will enable full, immediate, and continued Open Access for all work published in Journal of Neuroinflammation. The benefits from such Open Access will accrue to readers, through unrestricted access; to authors, through the widest possible dissemination of

  2. The microbiome: A key regulator of stress and neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kieran Rea

    2016-10-01

    In this review, the involvement of the gastrointestinal microbiota in stress-mediated and immune-mediated modulation of neuroendocrine, immune and neurotransmitter systems and the consequential behaviour is considered. We also focus on the mechanisms by which commensal gut microbiota can regulate neuroinflammation and further aim to exploit our understanding of their role in stress-related disorders as a consequence of neuroinflammatory processes.

  3. Does neuroinflammation fan the flame in neurodegenerative diseases?

    Directory of Open Access Journals (Sweden)

    McAlpine Fiona E

    2009-11-01

    Full Text Available Abstract While peripheral immune access to the central nervous system (CNS is restricted and tightly controlled, the CNS is capable of dynamic immune and inflammatory responses to a variety of insults. Infections, trauma, stroke, toxins and other stimuli are capable of producing an immediate and short lived activation of the innate immune system within the CNS. This acute neuroinflammatory response includes activation of the resident immune cells (microglia resulting in a phagocytic phenotype and the release of inflammatory mediators such as cytokines and chemokines. While an acute insult may trigger oxidative and nitrosative stress, it is typically short-lived and unlikely to be detrimental to long-term neuronal survival. In contrast, chronic neuroinflammation is a long-standing and often self-perpetuating neuroinflammatory response that persists long after an initial injury or insult. Chronic neuroinflammation includes not only long-standing activation of microglia and subsequent sustained release of inflammatory mediators, but also the resulting increased oxidative and nitrosative stress. The sustained release of inflammatory mediators works to perpetuate the inflammatory cycle, activating additional microglia, promoting their proliferation, and resulting in further release of inflammatory factors. Neurodegenerative CNS disorders, including multiple sclerosis (MS, Alzheimer's disease (AD, Parkinson's disease (PD, Huntington's disease (HD, amyotrophic lateral sclerosis (ALS, tauopathies, and age-related macular degeneration (ARMD, are associated with chronic neuroinflammation and elevated levels of several cytokines. Here we review the hallmarks of acute and chronic inflammatory responses in the CNS, the reasons why microglial activation represents a convergence point for diverse stimuli that may promote or compromise neuronal survival, and the epidemiologic, pharmacologic and genetic evidence implicating neuroinflammation in the

  4. Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease

    OpenAIRE

    Niels Andreasen; Kaj Blennow; Henrik Zetterberg

    2010-01-01

    Due to side effects in the form of meningoencephalitis in the interrupted phase II AN1792 trial of active antiamyloid ? (A ? ) immunization against Alzheimer's disease (AD), there has been concern that anti-A ? immunization may cause destructive neuroinflammation. Here, we report on two patients fulfilling clinical AD criteria who were diagnosed with Lyme neuroborreliosis during screening before inclusion in anti-A ? immunotherapy trials. The two cases illustrate the necessity of careful bioc...

  5. Role of neuroinflammation in hypertension-induced brain amyloid pathology.

    Science.gov (United States)

    Carnevale, Daniela; Mascio, Giada; Ajmone-Cat, Maria Antonietta; D'Andrea, Ivana; Cifelli, Giuseppe; Madonna, Michele; Cocozza, Germana; Frati, Alessandro; Carullo, Pierluigi; Carnevale, Lorenzo; Alleva, Enrico; Branchi, Igor; Lembo, Giuseppe; Minghetti, Luisa

    2012-01-01

    Hypertension and sporadic Alzheimer's disease (AD) have been associated but clear pathophysiological links have not yet been demonstrated. Hypertension and AD share inflammation as a pathophysiological trait. Thus, we explored if modulating neuroinflammation could influence hypertension-induced β-amyloid (Aβ) deposition. Possible interactions among hypertension, inflammation and Aβ-deposition were studied in hypertensive mice with transverse aortic coarctation (TAC). Given that brain Aβ deposits are detectable as early as 4 weeks after TAC, brain pathology was analyzed in 3-week TAC mice, before Aβ deposition, and at a later time (8-week TAC mice). Microglial activation and interleukin (IL)-1β upregulation were already found in 3-week TAC mice. At a later time, along with evident Aβ deposition, microglia was still activated. Finally, immune system stimulation (LPS) or inhibition (ibuprofen), strategies described to positively or negatively modulate neuroinflammation, differently affected Aβ deposition. We demonstrate that hypertension per se triggers neuroinflammation before Aβ deposition. The finding that only immune system activation, but not its inhibition, strongly reduced amyloid burden suggests that stimulating inflammation in the appropriate time window may represent a promising strategy to limit vascular-triggered AD-pathology. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Mevalonate Kinase Deficiency and Neuroinflammation: Balance between Apoptosis and Pyroptosis

    Directory of Open Access Journals (Sweden)

    Paola Maura Tricarico

    2013-11-01

    Full Text Available Mevalonic aciduria, a rare autosomal recessive disease, represents the most severe form of the periodic fever, known as Mevalonate Kinase Deficiency. This disease is caused by the mutation of the MVK gene, which codes for the enzyme mevalonate kinase, along the cholesterol pathway. Mevalonic aciduria patients show recurrent fever episodes with associated inflammatory symptoms, severe neurologic impairments, or death, in early childhood. The typical neurodegeneration occurring in mevalonic aciduria is linked both to the intrinsic apoptosis pathway (caspase-3 and -9, which is triggered by mitochondrial damage, and to pyroptosis (caspase-1. These cell death mechanisms seem to be also related to the assembly of the inflammasome, which may, in turn, activate pro-inflammatory cytokines and chemokines. Thus, this particular molecular platform may play a crucial role in neuroinflammation mechanisms. Nowadays, a specific therapy is still lacking and the pathogenic mechanisms involving neuroinflammation and neuronal dysfunction have not yet been completely understood, making mevalonic aciduria an orphan drug disease. This review aims to analyze the relationship among neuroinflammation, mitochondrial damage, programmed cell death, and neurodegeneration. Targeting inflammation and degeneration in the central nervous system might help identify promising treatment approaches for mevalonic aciduria or other diseases in which these mechanisms are involved.

  7. Dexmedetomidine reduces lipopolysaccharide induced neuroinflammation, sickness behavior, and anhedonia.

    Directory of Open Access Journals (Sweden)

    Ching-Hua Yeh

    Full Text Available Peripheral innate immune response may induce sickness behavior through activating microglia, excessive cytokines production, and neuroinflammation. Dexmedetomidine (Dex has anti-inflammatory effect. We investigated the effects of Dex on lipopolysaccharide (LPS-induced neuroinflammation and sickness behavior in mice.BALB/c mice were intraperitoneally (i.p. injected with Dex (50 ug/kg or vehicle. One hour later, the mice were injected (i.p. with Escherichia coli LPS (0.33 mg/kg or saline (n = 6 in each group. We analyzed the food and water intake, body weight loss, and sucrose preference of the mice for 24h. We also determined microglia activation and cytokines expression in the brains of the mice. In vitro, we determine cytokines expression in LPS-treated BV-2 microglial cells with or without Dex treatment.In the Dex-pretreated mice, LPS-induced sickness behavior (anorexia, weight loss, and social withdrawal were attenuated and microglial activation was lower than vehicle control. The mRNA expression of TNF-α, MCP-1, indoleamine 2, 3 dioxygenase (IDO, caspase-3, and iNOS were increased in the brain of LPS-challenged mice, which were reduced by Dex but not vehicle.Dexmedetomidine diminished LPS-induced neuroinflammation in the mouse brain and modulated the cytokine-associated changes in sickness behavior.

  8. DEVELOPMENT OF STRUCTURAL ADHESIVES,

    Science.gov (United States)

    Contents: (A) Structural adhesives for metals; development of better adhesives; development of heat resistance adhesives; development of room...temperature setting adhesives; recent investigations of metal-bonding adhesives; development of production processes and design criteria for metal adhesives... development of non-destructive inspection methods for adhesive bonded structures. (B) European papers; British developments in the field of

  9. Caffeine prevents d-galactose-induced cognitive deficits, oxidative stress, neuroinflammation and neurodegeneration in the adult rat brain.

    Science.gov (United States)

    Ullah, Faheem; Ali, Tahir; Ullah, Najeeb; Kim, Myeong Ok

    2015-11-01

    d-galactose has been considered a senescent model for age-related neurodegenerative disease. It induces oxidative stress which triggers memory impairment, neuroinflammation and neurodegeneration. Caffeine act as anti-oxidant and has been used in various model of neurodegenerative disease. Nevertheless, the effect of caffeine against d-galactose aging murine model of age-related neurodegenerative disease elucidated. Here, we investigated the neuroprotective effect of caffeine against d-galactose. We observed that chronic treatment of caffeine (3 mg/kg/day intraperitoneally (i.p) for 60 days) improved memory impairment and synaptic markers (Synaptophysin and PSD95) in the d-galactose treated rats. Chronic caffeine treatment reduced the oxidative stress via the reduction of 8-oxoguanine through immunofluorescence in the d-galactose-treated rats. Consequently caffeine treatment suppressed stress kinases p-JNK. Additionally, caffeine treatment significantly reduced the d-galactose-induced neuroinflammation through alleviation of COX-2, NOS-2, TNFα and IL-1β. Furthermore we also analyzed that caffeine reduced cytochrome C, Bax/Bcl2 ratio, caspase-9, caspase-3 and PARP-1 level. Moreover by evaluating the immunohistochemical results of Nissl and Fluro-Jade B staining showed that caffeine prevented the neurodegeneration in the d-galactose-treated rats. Our results showed that caffeine prevents the d-galactose-induced oxidative stress and consequently alleviated neuroinflammation and neurodegeneration; and synaptic dysfunction and memory impairment. Therefore, we could suggest that caffeine might be a dietary anti-oxidant agent and a good candidate for the age-related neurodegenerative disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Intranasal post-cardiac arrest treatment with orexin-A facilitates arousal from coma and ameliorates neuroinflammation.

    Science.gov (United States)

    Modi, Hiren R; Wang, Qihong; Gd, Sahithi; Sherman, David; Greenwald, Elliot; Savonenko, Alena V; Geocadin, Romergryko G; Thakor, Nitish V

    2017-01-01

    Cardiac arrest (CA) entails significant risks of coma resulting in poor neurological and behavioral outcomes after resuscitation. Significant subsequent morbidity and mortality in post-CA patients are largely due to the cerebral and cardiac dysfunction that accompanies prolonged whole-body ischemia post-CA syndrome (PCAS). PCAS results in strong inflammatory responses including neuroinflammation response leading to poor outcome. Currently, there are no proven neuroprotective therapies to improve post-CA outcomes apart from therapeutic hypothermia. Furthermore, there are no acceptable approaches to promote cortical or cognitive arousal following successful return of spontaneous circulation (ROSC). Hypothalamic orexinergic pathway is responsible for arousal and it is negatively affected by neuroinflammation. However, whether activation of the orexinergic pathway can curtail neuroinflammation is unknown. We hypothesize that targeting the orexinergic pathway via intranasal orexin-A (ORXA) treatment will enhance arousal from coma and decrease the production of proinflammatory cytokines resulting in improved functional outcome after resuscitation. We used a highly validated CA rat model to determine the effects of intranasal ORXA treatment 30-minute post resuscitation. At 4hrs post-CA, the mRNA levels of proinflammatory markers (IL1β, iNOS, TNF-α, GFAP, CD11b) and orexin receptors (ORX1R and ORX2R) were examined in different brain regions. CA dramatically increased proinflammatory markers in all brain regions particularly in the prefrontal cortex, hippocampus and hypothalamus. Post-CA intranasal ORXA treatment significantly ameliorated the CA-induced neuroinflammatory markers in the hypothalamus. ORXA administration increased production of orexin receptors (ORX1R and ORX2R) particularly in hypothalamus. In addition, ORXA also resulted in early arousal as measured by quantitative electroencephalogram (EEG) markers, and recovery of the associated behavioral neurologic

  11. Adenosine A2A Receptors Modulate Acute Injury and Neuroinflammation in Brain Ischemia

    Directory of Open Access Journals (Sweden)

    Felicita Pedata

    2014-01-01

    Full Text Available The extracellular concentration of adenosine in the brain increases dramatically during ischemia. Adenosine A2A receptor is expressed in neurons and glial cells and in inflammatory cells (lymphocytes and granulocytes. Recently, adenosine A2A receptor emerged as a potential therapeutic attractive target in ischemia. Ischemia is a multifactorial pathology characterized by different events evolving in the time. After ischemia the early massive increase of extracellular glutamate is followed by activation of resident immune cells, that is, microglia, and production or activation of inflammation mediators. Proinflammatory cytokines, which upregulate cell adhesion molecules, exert an important role in promoting recruitment of leukocytes that in turn promote expansion of the inflammatory response in ischemic tissue. Protracted neuroinflammation is now recognized as the predominant mechanism of secondary brain injury progression. A2A receptors present on central cells and on blood cells account for important effects depending on the time-related evolution of the pathological condition. Evidence suggests that A2A receptor antagonists provide early protection via centrally mediated control of excessive excitotoxicity, while A2A receptor agonists provide protracted protection by controlling massive blood cell infiltration in the hours and days after ischemia. Focus on inflammatory responses provides for adenosine A2A receptor agonists a wide therapeutic time-window of hours and even days after stroke.

  12. Therapeutic attenuation of neuroinflammation and apoptosis by black tea theaflavin in chronic MPTP/probenecid model of Parkinson's disease.

    Science.gov (United States)

    Anandhan, Annadurai; Essa, Musthafa Mohamed; Manivasagam, Thamilarasan

    2013-02-01

    Neuroinflammation and apoptosis in the dopaminergic neurons of substantia nigra play an important role in the pathogenesis of experimental and clinical Parkinson's disease (PD). This study focused on the possible anti-inflammatory and anti-apoptotic effects of theaflavin (TF), a black tea polyphenol against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. C57BL/6 male mice were treated with 10 doses of MPTP (25 mg/kg, s.c.) and probenecid (250 mg/kg, i.p.) for 3.5 days interval. TF (10 mg/kg) was administered 1 h prior to the administration of MPTP for 35 days of experimental period. MPTP/p treatment upregulates the release of interleukin-1beta, IL-6, tumor necrosis factor-alpha, IL-10, glial fibrillary acidic protein and Bax, and downregulates anti-apoptotic marker Bcl-2. Oral treatment of black tea polyphenol TF significantly attenuates MPTP-induced neuroinflammation as well as apoptosis. Behavioral studies (catalepsy and akinesia) were carried out to confirm these molecular studies. The results demonstrate that TF mediated its neuroprotection against chronic MPTP-induced toxicity through the involvement of multiple molecular events. It was concluded that TF may provide a precious therapeutic strategy for the treatment of progressive neurodegenerative disease such as PD in future.

  13. Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation.

    Science.gov (United States)

    Chanana, Priyanka; Kumar, Anil

    2016-04-01

    Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF α level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice. Copyright © 2016 John Wiley & Sons, Ltd.

  14. Aromatase and neuroinflammation in rat focal brain ischemia.

    Science.gov (United States)

    Zhong, Yu H; Dhawan, Jasbeer; Kovoor, Joel A; Sullivan, John; Zhang, Wei X; Choi, Dennis; Biegon, Anat

    2017-11-01

    Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents. Intact male rats were subjected to transient (90min) middle cerebral artery occlusion (MCAO) and administered selfotel (N-methyl-d-aspartic acid (NMDA) receptor competitive antagonist), TPEN (a zinc chelator), a combination of the two drugs or vehicle, injected immediately after reperfusion. Animals were killed 14days after MCAO and consecutive brain sections used to measure aromatase expression, cerebral infarct volume and neuroinflammation. Quantitative immunohistochemistry (IHC) demonstrated increased brain aromatase expression in the peri-infarct area relative to contralesional area, which was partially abrogated by neuroprotective agents. There was no correlation between aromatase expression in the peri-infarct zone and infarct volume, which was reduced by neuroprotective agents. Microglial activation, measured by quantitative autoradiography, was positively correlated with infarct and inversely correlated with aromatase expression in the peri-infarct zone. Our findings indicate that focal ischemia upregulates brain aromatase in the male rat brain at 14days post surgery, which is within the time frame documented in females. However, the lack of negative correlation between aromatase expression and infarct volume and lack of positive correlation between microgliosis and aromatase do not support a major role for aromatase as a mediator of neuroprotection or a causal relationship between microglial activation and increased aromatase

  15. Bacterial Adhesion & Blocking Bacterial Adhesion

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk

    2008-01-01

    components. These substances may both mediate and stabilize the bacterial biofilm. Finally, several adhesive structures were examined, and a novel physiological biofilm phenotype in E.coli biofilms was characterized, namely cell chain formation. The autotransporter protein, antigen 43, was implicated...

  16. Adhesive plasters

    Science.gov (United States)

    Holcombe, Jr., Cressie E.; Swain, Ronald L.; Banker, John G.; Edwards, Charlene C.

    1978-01-01

    Adhesive plaster compositions are provided by treating particles of Y.sub.2 O.sub.3, Eu.sub.2 O.sub.3, Gd.sub.2 O.sub.3 or Nd.sub.2 O.sub.3 with dilute acid solutions. The resulting compositions have been found to spontaneously harden into rigid reticulated masses resembling plaster of Paris. Upon heating, the hardened material is decomposed into the oxide, yet retains the reticulated rigid structure.

  17. Punicalagin inhibits neuroinflammation in LPS-activated rat primary microglia.

    Science.gov (United States)

    Olajide, Olumayokun A; Kumar, Asit; Velagapudi, Ravikanth; Okorji, Uchechukwu P; Fiebich, Bernd L

    2014-09-01

    In this study, the effects of punicalagin on neuroinflammation in LPS-activated microglia were investigated. The ability of punicalagin to reduce the production of TNF-α, IL-6 and prostaglandin E2 was measured in culture medium using enzyme immunoassay. TNF-α and IL-6 gene expression in mouse hippocampal slices was measured with PCR. cyclooxygenase-2 and microsomal prostaglandin E synthase 1 protein and mRNA were evaluated with Western blotting and PCR, respectively. Further experiments to investigate effects of punicalagin on protein expressions of inflammatory targets were also determined with Western blotting. Pretreatment of rat primary microglia with punicalagin (5-40 μM) prior to LPS (10 ng/mL) stimulation produced a significant (p Punicalagin completely abolished TNF-α and IL-6 gene expression in LPS-stimulated hippocampal slices. Protein and mRNA expressions of cyclooxygenase-2 and microsomal prostaglandin E synthase 1 were also reduced by punicalagin pretreatment. Results show that punicalagin interferes with NF-κB signalling through attenuation of NF-κB-driven luciferase expression, as well as inhibition of IκB phosphorylation and nuclear translocation of p65 subunit in the microglia. These results suggest that punicalagin inhibits neuroinflammation in LPS-activated microglia through interference with NF-κB signalling, suggesting its potential as a nutritional preventive strategy in neurodegenerative disorders. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy.

    Science.gov (United States)

    Cherry, Jonathan D; Tripodis, Yorghos; Alvarez, Victor E; Huber, Bertrand; Kiernan, Patrick T; Daneshvar, Daniel H; Mez, Jesse; Montenigro, Philip H; Solomon, Todd M; Alosco, Michael L; Stern, Robert A; McKee, Ann C; Stein, Thor D

    2016-10-28

    The chronic effects of repetitive head impacts (RHI) on the development of neuroinflammation and its relationship to chronic traumatic encephalopathy (CTE) are unknown. Here we set out to determine the relationship between RHI exposure, neuroinflammation, and the development of hyperphosphorylated tau (ptau) pathology and dementia risk in CTE. We studied a cohort of 66 deceased American football athletes from the Boston University-Veteran's Affairs-Concussion Legacy Foundation Brain Bank as well as 16 non-athlete controls. Subjects with a neurodegenerative disease other than CTE were excluded. Counts of total and activated microglia, astrocytes, and ptau pathology were performed in the dorsolateral frontal cortex (DLF). Binary logistic and simultaneous equation regression models were used to test associations between RHI exposure, microglia, ptau pathology, and dementia. Duration of RHI exposure and the development and severity of CTE were associated with reactive microglial morphology and increased numbers of CD68 immunoreactive microglia in the DLF. A simultaneous equation regression model demonstrated that RHI exposure had a significant direct effect on CD68 cell density (p chronic activation of microglia, which may partially mediate the effect of RHI on the development of ptau pathology and dementia in CTE. Inflammatory molecules may be important diagnostic or predictive biomarkers as well as promising therapeutic targets in CTE.

  19. Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease.

    Science.gov (United States)

    Moussa, Charbel; Hebron, Michaeline; Huang, Xu; Ahn, Jaeil; Rissman, Robert A; Aisen, Paul S; Turner, R Scott

    2017-01-03

    Treatment of mild-moderate Alzheimer's disease (AD) subjects (N = 119) for 52 weeks with the SIRT1 activator resveratrol (up to 1 g by mouth twice daily) attenuates progressive declines in CSF Aβ40 levels and activities of daily living (ADL) scores. For this retrospective study, we examined banked CSF and plasma samples from a subset of AD subjects with CSF Aβ42 resveratrol-treated and N = 19 placebo-treated). We utilized multiplex Xmap technology to measure markers of neurodegenerative disease and metalloproteinases (MMPs) in parallel in CSF and plasma samples. Compared to the placebo-treated group, at 52 weeks, resveratrol markedly reduced CSF MMP9 and increased macrophage-derived chemokine (MDC), interleukin (IL)-4, and fibroblast growth factor (FGF)-2. Compared to baseline, resveratrol increased plasma MMP10 and decreased IL-12P40, IL12P70, and RANTES. In this subset analysis, resveratrol treatment attenuated declines in mini-mental status examination (MMSE) scores, change in ADL (ADCS-ADL) scores, and CSF Aβ42 levels during the 52-week trial, but did not alter tau levels. Collectively, these data suggest that resveratrol decreases CSF MMP9, modulates neuro-inflammation, and induces adaptive immunity. SIRT1 activation may be a viable target for treatment or prevention of neurodegenerative disorders. ClinicalTrials.gov NCT01504854.

  20. Parasitic manipulation and neuroinflammation: Evidence from the system Microphallus papillorobustus (Trematoda - Gammarus (Crustacea

    Directory of Open Access Journals (Sweden)

    Thomas Frederic

    2010-04-01

    Full Text Available Abstract Background Neuropathological consequences of neuroinflammatory processes have been implicated in a wide range of diseases affecting the central nervous system (CNS. Glial cells, the resident immune cells of the CNS, respond to tissue injury by releasing proinflammatory cytokines and free radicals such as nitric oxide. We explored the possibility that neuroimmune responses are involved in parasitic manipulation of host behavior in a trematode-crustacean association. The cerebral larva of the flatworm Microphallus papillorobustus alters responses to environmental stimuli - and thus reflex pathways - in the crustacean Gammarus insensibilis, in a way that enhances predation of the crustacean by birds, definitive hosts of the parasite. Results Immunocytochemical experiments followed by confocal microscopy were performed to study the distribution of glutamine synthetase, a glial cell marker, and nitric oxide synthase in the brain of gammarids. Astrocyte-like glia and their processes were abundant at the surface of the parasites while levels of nitric oxide synthase were elevated at the host-parasite interface in the brain of gammarids harboring mature cerebral larvae and demonstrating altered behavior. Conclusion Taken together these results lend support to the neuroinflammation hypothesis whereby a chronic CNS specific immune response induced by the parasite plays a role in the disruption of neuromodulation, neuronal integrity, and behavior in infected hosts.

  1. Parasitic manipulation and neuroinflammation: Evidence from the system Microphallus papillorobustus (Trematoda) - Gammarus (Crustacea)

    Science.gov (United States)

    2010-01-01

    Background Neuropathological consequences of neuroinflammatory processes have been implicated in a wide range of diseases affecting the central nervous system (CNS). Glial cells, the resident immune cells of the CNS, respond to tissue injury by releasing proinflammatory cytokines and free radicals such as nitric oxide. We explored the possibility that neuroimmune responses are involved in parasitic manipulation of host behavior in a trematode-crustacean association. The cerebral larva of the flatworm Microphallus papillorobustus alters responses to environmental stimuli - and thus reflex pathways - in the crustacean Gammarus insensibilis, in a way that enhances predation of the crustacean by birds, definitive hosts of the parasite. Results Immunocytochemical experiments followed by confocal microscopy were performed to study the distribution of glutamine synthetase, a glial cell marker, and nitric oxide synthase in the brain of gammarids. Astrocyte-like glia and their processes were abundant at the surface of the parasites while levels of nitric oxide synthase were elevated at the host-parasite interface in the brain of gammarids harboring mature cerebral larvae and demonstrating altered behavior. Conclusion Taken together these results lend support to the neuroinflammation hypothesis whereby a chronic CNS specific immune response induced by the parasite plays a role in the disruption of neuromodulation, neuronal integrity, and behavior in infected hosts. PMID:20398322

  2. Adhesion and Cohesion

    Directory of Open Access Journals (Sweden)

    J. Anthony von Fraunhofer

    2012-01-01

    Full Text Available The phenomena of adhesion and cohesion are reviewed and discussed with particular reference to dentistry. This review considers the forces involved in cohesion and adhesion together with the mechanisms of adhesion and the underlying molecular processes involved in bonding of dissimilar materials. The forces involved in surface tension, surface wetting, chemical adhesion, dispersive adhesion, diffusive adhesion, and mechanical adhesion are reviewed in detail and examples relevant to adhesive dentistry and bonding are given. Substrate surface chemistry and its influence on adhesion, together with the properties of adhesive materials, are evaluated. The underlying mechanisms involved in adhesion failure are covered. The relevance of the adhesion zone and its importance with regard to adhesive dentistry and bonding to enamel and dentin is discussed.

  3. Cannabinoids and Innate Immunity: Taking a Toll on Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Eric J. Downer

    2011-01-01

    Full Text Available The biologically active components of cannabis have therapeutic potential in neuroinflammatory disorders due to their anti-inflammatory propensity. Cannabinoids influence immune function in both the peripheral and the central nervous system (CNS, and the components of the cannabinoid system, the cannabinoid receptors and their endogenous ligands (endocannabinoids, have been detected on immune cells as well as in brain glia. Neuroinflammation is the complex innate immune response of neural tissue to control infection and eliminate pathogens, and Toll-like receptors (TLRs, a major family of pattern recognition receptors (PRRs that mediate innate immunity, have emerged as players in the neuroinflammatory processes underpinning various CNS diseases. This review will highlight evidence that cannabinoids interact with the immune system by impacting TLR-mediated signaling events, which may provide cues for devising novel therapeutic approaches for cannabinoid ligands.

  4. Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Niels Andreasen

    2010-01-01

    Full Text Available Due to side effects in the form of meningoencephalitis in the interrupted phase II AN1792 trial of active antiamyloid β(Aβ immunization against Alzheimer's disease (AD, there has been concern that anti-Aβ immunization may cause destructive neuroinflammation. Here, we report on two patients fulfilling clinical AD criteria who were diagnosed with Lyme neuroborreliosis during screening before inclusion in anti-Aβ immunotherapy trials. The two cases illustrate the necessity of careful biochemical screening for neuroinflammatory/neuroinfectious conditions before an AD diagnosis is made and before clinical AD patients are included in trials of therapy that could impact the immune system. Should the two cases have been included and deteriorated, additional investigations might have led to the erroneous conclusion that therapy-induced meningoencephalitis had occurred.

  5. Neuroinflammation Screening in Immunotherapy Trials against Alzheimer's Disease.

    Science.gov (United States)

    Andreasen, Niels; Blennow, Kaj; Zetterberg, Henrik

    2010-12-19

    Due to side effects in the form of meningoencephalitis in the interrupted phase II AN1792 trial of active antiamyloid β(Aβ) immunization against Alzheimer's disease (AD), there has been concern that anti-Aβ immunization may cause destructive neuroinflammation. Here, we report on two patients fulfilling clinical AD criteria who were diagnosed with Lyme neuroborreliosis during screening before inclusion in anti-Aβ immunotherapy trials. The two cases illustrate the necessity of careful biochemical screening for neuroinflammatory/neuroinfectious conditions before an AD diagnosis is made and before clinical AD patients are included in trials of therapy that could impact the immune system. Should the two cases have been included and deteriorated, additional investigations might have led to the erroneous conclusion that therapy-induced meningoencephalitis had occurred.

  6. Molecular mechanisms of neuroinflammation and injury during acute viral encephalitis.

    Science.gov (United States)

    Shives, Katherine D; Tyler, Kenneth L; Beckham, J David

    2017-07-15

    Viral infections in the central nervous system are a major cause of encephalitis. West Nile virus (WNV) and Herpes simplex virus (HSV) are the most common causes of viral encephalitis in the United States. We review the role of neuroinflammation in the pathogenesis of WNV and HSV infections in the central nervous system (CNS). We discuss the role of the innate and cell-mediated immune responses in peripheral control of viral infection, viral invasion of the CNS, and in inflammatory-mediated neuronal injury. By understanding the role of specific inflammatory responses to viral infections in the CNS, targeted therapeutic approaches can be developed to maximize control of acute viral infection while minimizing neuronal injury in the CNS. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Mutant huntingtin gene-dose impacts on aggregate deposition, DARPP32 expression and neuroinflammation in HdhQ150 mice.

    Directory of Open Access Journals (Sweden)

    Douglas Young

    Full Text Available Huntington's disease (HD is an autosomal dominant, progressive and fatal neurological disorder caused by an expansion of CAG repeats in exon-1 of the huntingtin gene. The encoded poly-glutamine stretch renders mutant huntingtin prone to aggregation. HdhQ150 mice genocopy a pathogenic repeat (∼150 CAGs in the endogenous mouse huntingtin gene and model predominantly pre-manifest HD. Treating early is likely important to prevent or delay HD, and HdhQ150 mice may be useful to assess therapeutic strategies targeting pre-manifest HD. This requires appropriate markers and here we demonstrate, that pre-symptomatic HdhQ150 mice show several dramatic mutant huntingtin gene-dose dependent pathological changes including: (i an increase of neuronal intra-nuclear inclusions (NIIs in brain, (ii an increase of extra-nuclear aggregates in dentate gyrus, (iii a decrease of DARPP32 protein and (iv an increase in glial markers of neuroinflammation, which curiously did not correlate with local neuronal mutant huntingtin inclusion-burden. HdhQ150 mice developed NIIs also in all retinal neuron cell-types, demonstrating that retinal NIIs are not specific to human exon-1 R6 HD mouse models. Taken together, the striking and robust mutant huntingtin gene-dose related changes in aggregate-load, DARPP32 levels and glial activation markers should greatly facilitate future testing of therapeutic strategies in the HdhQ150 HD mouse model.

  8. Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

    Directory of Open Access Journals (Sweden)

    Jia Liu

    2017-08-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disease that affects upper motor neurons (MNs comprising the corticospinal tract and lower MNs arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease.

  9. Role of Neuroinflammation in Amyotrophic Lateral Sclerosis: Cellular Mechanisms and Therapeutic Implications

    Science.gov (United States)

    Liu, Jia; Wang, Fei

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects upper motor neurons (MNs) comprising the corticospinal tract and lower MNs arising from the brain stem nuclei and ventral roots of the spinal cord, leading to fatal paralysis. Currently, there are no effective therapies for ALS. Increasing evidence indicates that neuroinflammation plays an important role in ALS pathogenesis. The neuroinflammation in ALS is characterized by infiltration of lymphocytes and macrophages, activation of microglia and reactive astrocytes, as well as the involvement of complement. In this review, we focus on the key cellular players of neuroinflammation during the pathogenesis of ALS by discussing not only their detrimental roles but also their immunomodulatory actions. We will summarize the pharmacological therapies for ALS that target neuroinflammation, as well as recent advances in the field of stem cell therapy aimed at modulating the inflammatory environment to preserve the remaining MNs in ALS patients and animal models of the disease. PMID:28871262

  10. [18F]DPA 714 PET Imaging Reveals Global Neuroinflammation in Zika Virus Infected Mice

    Science.gov (United States)

    2017-09-12

    with neurotropic viruses and the evaluation of therapeutics being developed for treatment of infectious diseases. Keywords: Zika virus , Animal...18F]DPA-714 PET Imaging Reveals Global Neuroinflammation in Zika Virus - Infected Mice Kyle Kuszpit1†, Bradley S. Hollidge2†, Xiankun Zeng3, Robert...Running Head: PET Imaging of Zika Virus -Induced Neuroinflammation Manuscript Category: Article Affiliations: 1Molecular and Translational

  11. Direct Test for Neuroinflammation with [11C]DAP-713-PET Scanning

    Science.gov (United States)

    2016-10-01

    will be undertaken at Johns Hopkins. 15. SUBJECT TERMS molecular imaging; PET; Gulf War Illness; DPA-713; distribution volume; neuroinflammation 16...KEYWORDS: molecular imaging; PET; Gulf War Illness; DPA-713; distribution volume; neuroinflammation ACCOMPLISHMENTS: What were the major goals of...support of the PD/PI(s) or senior/key personnel since the last reporting period?  Martin Pomper Ended Title: PSMA-associated PET imaging of CAR T

  12. Targeting Extracellular Cyclophilin A Reduces Neuroinflammation and Extends Survival in a Mouse Model of Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Pasetto, Laura; Pozzi, Silvia; Castelnovo, Mariachiara; Basso, Manuela; Estevez, Alvaro G; Fumagalli, Stefano; De Simoni, Maria Grazia; Castellaneta, Valeria; Bigini, Paolo; Restelli, Elena; Chiesa, Roberto; Trojsi, Francesca; Monsurrò, Maria Rosaria; Callea, Leonardo; Malešević, Miroslav; Fischer, Gunter; Freschi, Mattia; Tortarolo, Massimo; Bendotti, Caterina; Bonetto, Valentina

    2017-02-08

    Neuroinflammation is a major hallmark of amyotrophic lateral sclerosis (ALS), which is currently untreatable. Several anti-inflammatory compounds have been evaluated in patients and in animal models of ALS, but have been proven disappointing in part because effective targets have not yet been identified. Cyclophilin A, also known as peptidylprolyl cis-/trans-isomerase A (PPIA), as a foldase is beneficial intracellularly, but extracellularly has detrimental functions. We found that extracellular PPIA is a mediator of neuroinflammation in ALS. It is a major inducer of matrix metalloproteinase 9 and is selectively toxic for motor neurons. High levels of PPIA were found in the CSF of SOD1G93A mice and rats and sporadic ALS patients, suggesting that our findings may be relevant for familial and sporadic cases. A specific inhibitor of extracellular PPIA, MM218, given at symptom onset, rescued motor neurons and extended survival in the SOD1G93A mouse model of familial ALS by 11 d. The treatment resulted in the polarization of glia toward a prohealing phenotype associated with reduced NF-κB activation, proinflammatory markers, endoplasmic reticulum stress, and insoluble phosphorylated TDP-43. Our results indicates that extracellular PPIA is a promising druggable target for ALS and support further studies to develop a therapy to arrest or slow the progression of the disease in patients.SIGNIFICANCE STATEMENT We provide evidence that extracellular cyclophilin A, also known as peptidylprolyl cis-/trans-isomerase A (PPIA), is a mediator of the neuroinflammatory reaction in amyotrophic lateral sclerosis (ALS) and is toxic for motor neurons. Supporting this, a specific extracellular PPIA inhibitor reduced neuroinflammation, rescued motor neurons, and extended survival in the SOD1G93A mouse model of familial ALS. Our findings suggest selective pharmacological inhibition of extracellular PPIA as a novel therapeutic strategy, not only for SOD1-linked ALS, but possibly also for

  13. Neuroinflammation is not a prerequisite for diabetes-induced tau phosphorylation

    Directory of Open Access Journals (Sweden)

    Judith M Van Der Harg

    2015-11-01

    Full Text Available Abnormal phosphorylation and aggregation of tau is a key hallmark of Alzheimer's disease (AD. AD is a multifactorial neurodegenerative disorder for which Diabetes Mellitus (DM is a risk factor. In animal models for DM, the phosphorylation and aggregation of tau is induced or exacerbated, however the underlying mechanism is unknown. In addition to the metabolic dysfunction, DM is characterized by chronic low-grade inflammation. This was reported to be associated with a neuroinflammatory response in the hypothalamus of DM animal models. Neuroinflammation is also implicated in the development and progression of AD. It is unknown whether DM also induces neuroinflammation in brain areas affected in AD, the cortex and hippocampus. Here we investigated whether neuroinflammation could be the mechanistic trigger to induce tau phosphorylation in the brain of DM animals. Two distinct diabetic animal models were used; rats on free-choice high-fat high-sugar (fcHFHS diet that are insulin resistant and streptozotocin-treated rats that are insulin deficient. The streptozotocin-treated animals demonstrated increased tau phosphorylation in the brain as expected, whereas the fcHFHS diet fed animals did not. Remarkably, neither of the diabetic animal models showed reactive microglia or increased GFAP and COX-2 levels in the cortex or hippocampus. From this, we conclude: 1. DM does not induce neuroinflammation in brain regions affected in AD, and 2. Neuroinflammation is not a prerequisite for tau phosphorylation. Neuroinflammation is therefore not the mechanism that explains the close connection between DM and AD.

  14. Adhesion in microelectronics

    CERN Document Server

    Mittal, K L

    2014-01-01

    This comprehensive book will provide both fundamental and applied aspects of adhesion pertaining to microelectronics in a single and easily accessible source. Among the topics to be covered include; Various theories or mechanisms of adhesionSurface (physical or chemical) characterization of materials as it pertains to adhesionSurface cleaning as it pertains to adhesionWays to improve adhesionUnraveling of interfacial interactions using an array of pertinent techniquesCharacterization of interfaces / interphasesPolymer-polymer adhesionMetal-polymer adhesion  (metallized polymers)Polymer adhesi

  15. Withania somnifera as a potential candidate to ameliorate high fat diet-induced anxiety and neuroinflammation.

    Science.gov (United States)

    Kaur, Taranjeet; Kaur, Gurcharan

    2017-10-12

    The epidemic of obesity has reached alarming levels in both developing and developed nations. Excessive calorie intake and sedentary lifestyle due to technological advancements are the main causal factors for overweight and obesity among the human population. Obesity has been associated with a number of co-morbidities such as hypertension, type 2 diabetes mellitus, cardiovascular diseases, and neurodegeneration and dementia. The progression of neurological disorders in obese subjects has been mainly attributed to neuroinflammation. Withania somnifera has been used in numerous Ayurvedic formulations owing to its wide array of health-promoting properties. The current study was designed to test the hypothesis whether dry leaf powder of W. somnifera has anxiolytic and anti-neuroinflammatory potential in diet-induced obesity. Young adult female rats were divided into four groups: low fat diet group (LFD) fed with regular chow feed, high fat diet group (HFD) fed with diet containing 30% fat by weight, low fat diet plus extract group (LFDE) fed with regular chow feed supplemented with dry leaf powder of W. somnifera 1 mg/g of body weight (ASH), and high fat diet plus extract group (HFDE) fed with diet containing 30% fat by weight and supplemented with ASH. All the animals were kept on respective feeding regimen for 12 weeks; following which, the animals were tested for their anxiety-like behavior using elevated plus maze test. The animals were sacrificed and used to study various inflammatory markers such as GFAP, Iba1, PPARγ, iNOS, MCP-1, TNFα, IL-1β, IL-6, and various markers of NF-κB pathway by Western blotting and quantitative real-time PCR. Serum levels of leptin, insulin and pro-inflammatory cytokines were also assayed. ASH treated rats showed less anxiety levels as compared to HFD animals. At molecular level, ASH ameliorated the HFD-induced reactive gliosis and microgliosis and suppressed the expression of inflammatory markers such as PPARγ, iNOS, MCP-1

  16. Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

    Science.gov (United States)

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2014-01-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

  17. Microglia Morphological Categorization in a Rat Model of Neuroinflammation by Hierarchical Cluster and Principal Components Analysis.

    Science.gov (United States)

    Fernández-Arjona, María Del Mar; Grondona, Jesús M; Granados-Durán, Pablo; Fernández-Llebrez, Pedro; López-Ávalos, María D

    2017-01-01

    It is known that microglia morphology and function are closely related, but only few studies have objectively described different morphological subtypes. To address this issue, morphological parameters of microglial cells were analyzed in a rat model of aseptic neuroinflammation. After the injection of a single dose of the enzyme neuraminidase (NA) within the lateral ventricle (LV) an acute inflammatory process occurs. Sections from NA-injected animals and sham controls were immunolabeled with the microglial marker IBA1, which highlights ramifications and features of the cell shape. Using images obtained by section scanning, individual microglial cells were sampled from various regions (septofimbrial nucleus, hippocampus and hypothalamus) at different times post-injection (2, 4 and 12 h). Each cell yielded a set of 15 morphological parameters by means of image analysis software. Five initial parameters (including fractal measures) were statistically different in cells from NA-injected rats (most of them IL-1β positive, i.e., M1-state) compared to those from control animals (none of them IL-1β positive, i.e., surveillant state). However, additional multimodal parameters were revealed more suitable for hierarchical cluster analysis (HCA). This method pointed out the classification of microglia population in four clusters. Furthermore, a linear discriminant analysis (LDA) suggested three specific parameters to objectively classify any microglia by a decision tree. In addition, a principal components analysis (PCA) revealed two extra valuable variables that allowed to further classifying microglia in a total of eight sub-clusters or types. The spatio-temporal distribution of these different morphotypes in our rat inflammation model allowed to relate specific morphotypes with microglial activation status and brain location. An objective method for microglia classification based on morphological parameters is proposed. Main points Microglia undergo a quantifiable

  18. Region-Specific Vulnerability to Oxidative Stress, Neuroinflammation, and Tau Hyperphosphorylation in Experimental Diabetes Mellitus Mice.

    Science.gov (United States)

    Elahi, Montasir; Hasan, Zafrul; Motoi, Yumiko; Matsumoto, Shin-Ei; Ishiguro, Koichi; Hattori, Nobutaka

    2016-01-01

    Recent epidemiological evidence suggests that diabetes mellitus (DM) is a risk factor for Alzheimer's disease (AD). One of the pathological hallmarks of AD is hyperphosphorylated tau protein, which forms neurofibrillary tangles. Oxidative stress and the activation of inflammatory pathways are features that are associated with both DM and AD. However, the brain region specificity of AD-related neurodegeneration, which mainly occurs in the hippocampus while the cerebellum is relatively unaffected, has not yet been clarified. Therefore, we used experimental DM mice (caused by an intraperitoneal injection of streptozotocin [STZ]) to determine whether these neurodegeneration-associated mechanisms were associated with region-specific selective vulnerability or tau phosphorylation. The hippocampus, midbrain, and cerebellum of aged (14 to 18 months old) non-transgenic (NTg) and transgenic mice overexpressing wild-type human tau (Tg601 mice) were evaluated after a treatment with STZ. The STZ injection increased reactive oxygen species, lipid peroxidation markers such as 4-hydroxynonenal and malondialdehyde in the hippocampus, but not in the midbrain or cerebellum. The STZ treatment also increased the number of Iba-1-positive and CD68-positive microglial cells, astrocytes, and IL-1β, IL-6, IL-10, and IL-18 levels in the hippocampus, but not in the midbrain or cerebellum. Tau hyperphosphorylation was also enhanced in the hippocampus, but not in the midbrain or cerebellum. When the effects of STZ were compared between Tg601 and NTg mice, microglial proliferation and elevations in IL-6 and phosphorylated tau were higher in Tg601 mice. These results suggest that neuroinflammation and oxidative stress in STZ-treated mice are associated with tau hyperphosphorylation, which may contribute to selective neurodegeneration in human AD.

  19. Region-selective effects of neuroinflammation and antioxidant treatment on peripheral benzodiazepine receptors and NMDA receptors in the rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Biegon, A.; Alvarado, M.; Budinger, T.F.; Grossman, R.; Hensley, K.; West, M.S.; Kotake, Y.; Ono, M.; Floyd, R.A.

    2001-12-10

    Following induction of acute neuroinflammation by intracisternal injection of endotoxin (lipopolysaccharide) in rats, quantitative autoradiography was used to assess the regional level of microglial activation and glutamate (NMDA) receptor binding. The possible protective action of the antioxidant phenyl-tert-butyl nitrone in this model was tested by administering the drug in the drinking water for 6 days starting 24 hours after endotoxin injection. Animals were killed 7 days post-injection and consecutive cryostat brain sections labeled with [3H]PK11195 as a marker of activated microglia and [125I]iodoMK801 as a marker of the open-channel, activated state of NMDA receptors. Lipopolysaccharide increased [3H]PK11195 binding in the brain, with the largest increases (2-3 fold) in temporal and entorhinal cortex, hippocampus, and substantia innominata. A significant (>50 percent) decrease in [125I]iodoMK801 binding was found in the same brain regions. Phenyl-tert-butyl nitrone treatment resulted in a partial inhibition ({approx}25 percent decrease) of the lipopolysaccharide-induced increase in [3H]PK11195 binding but completely reversed the lipopolysaccharide-induced decrease in [125I]iodoMK80 binding in the entorhinal cortex, hippocampus, and substantia innominata. Loss of NMDA receptor function in cortical and hippocampal regions may contribute to the cognitive deficits observed in diseases with a neuroinflammatory component, such as meningitis or Alzheimer's disease.

  20. Puerarin Alleviates Neuropathic Pain by Inhibiting Neuroinflammation in Spinal Cord

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    Ming Liu

    2014-01-01

    Full Text Available Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4–100 nM for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.

  1. Neuroinflammation and brain functional disconnection in Alzheimer's disease

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    Francesca eBaglio

    2013-11-01

    Full Text Available Neuroinflammation and brain functional disconnection result from β-amyloid (Aβ accumulation and play fundamental roles in the pathogenesis of Alzheimer’s disease (AD. We investigated possible correlations between these two AD-associated phenomena using DTI-based tractography and immunologic analyses in people with amnestic Mild Cognitive Impairment (aMCI and AD. DTI-Analyses focused on corpus callosum (CC. We found that frontal CC regions were preserved with respect to the posterior ones in aMCI; in these individuals significant correlations were seen between DTI-derived metrics in frontal-parietal CC areas and Aβ42-stimulated BDNF-producing CD4+ T lymphocytes and PDL-1-expressing CD14+ cells. These associations were lost in AD where DTI data involving the same CC areas correlated instead with Aβ42-stimulated IL-21 producing CD4+ T lymphocytes. Higher susceptibility to PDL-1-mediated apoptosis of Aβ42-specific lymphocytes and BDNF-associated survival of existing neurons could contribute to the relative CC structure preservation seen in aMCI. These potentially protective mechanisms are lost in frank AD, when severe alterations in the CC are mirrored in peripheral blood by proinflammatory cytokines-producing T cells. Monitoring of immune cells in peripheral blood could have a prognostic value in AD.

  2. Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

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    Gertjan eVan Dijk

    2015-05-01

    Full Text Available Alzheimer’s disease (AD is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP to amyloid β peptide, tau protein hyperphosphorylation, relocalization and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by systems biology approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework.

  3. Neuroinflammation and Oxidative Stress in Psychosis and Psychosis Risk

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    Henry Barron

    2017-03-01

    Full Text Available Although our understanding of psychotic disorders has advanced substantially in the past few decades, very little has changed in the standard of care for these illnesses since the development of atypical anti-psychotics in the 1990s. Here, we integrate new insights into the pathophysiology with the increasing interest in early detection and prevention. First, we explore the role of N-methyl-d-aspartate receptors in a subpopulation of cortical parvalbumin-containing interneurons (PVIs. Postmortem and preclinical data has implicated these neurons in the positive and negative symptoms, as well as the cognitive dysfunction present in schizophrenia. These neurons also appear to be sensitive to inflammation and oxidative stress during the perinatal and peripubertal periods, which may be mediated in large part by aberrant synaptic pruning. After exploring some of the molecular mechanisms through which neuroinflammation and oxidative stress are thought to exert their effects, we highlight the progress that has been made in identifying psychosis prior to onset through the identification of individuals at clinical high risk for psychosis (CHR. By combining our understanding of psychosis pathogenesis with the increasing characterization of endophenotypes that precede frank psychosis, it may be possible to identify patients before they present with psychosis and intervene to reduce the burden of the disease to both patients and families.

  4. Neuroinflammation and Oxidative Stress in Psychosis and Psychosis Risk.

    Science.gov (United States)

    Barron, Henry; Hafizi, Sina; Andreazza, Ana C; Mizrahi, Romina

    2017-03-17

    Although our understanding of psychotic disorders has advanced substantially in the past few decades, very little has changed in the standard of care for these illnesses since the development of atypical anti-psychotics in the 1990s. Here, we integrate new insights into the pathophysiology with the increasing interest in early detection and prevention. First, we explore the role of N -methyl-d-aspartate receptors in a subpopulation of cortical parvalbumin-containing interneurons (PVIs). Postmortem and preclinical data has implicated these neurons in the positive and negative symptoms, as well as the cognitive dysfunction present in schizophrenia. These neurons also appear to be sensitive to inflammation and oxidative stress during the perinatal and peripubertal periods, which may be mediated in large part by aberrant synaptic pruning. After exploring some of the molecular mechanisms through which neuroinflammation and oxidative stress are thought to exert their effects, we highlight the progress that has been made in identifying psychosis prior to onset through the identification of individuals at clinical high risk for psychosis (CHR). By combining our understanding of psychosis pathogenesis with the increasing characterization of endophenotypes that precede frank psychosis, it may be possible to identify patients before they present with psychosis and intervene to reduce the burden of the disease to both patients and families.

  5. Understanding Marine Mussel Adhesion

    Energy Technology Data Exchange (ETDEWEB)

    H. G. Silverman; F. F. Roberto

    2007-12-01

    In addition to identifying the proteins that have a role in underwater adhesion by marine mussels, research efforts have focused on identifying the genes responsible for the adhesive proteins, environmental factors that may influence protein production, and strategies for producing natural adhesives similar to the native mussel adhesive proteins. The production-scale availability of recombinant mussel adhesive proteins will enable researchers to formulate adhesives that are waterimpervious and ecologically safe and can bind materials ranging from glass, plastics, metals, and wood to materials, such as bone or teeth, biological organisms, and other chemicals or molecules. Unfortunately, as of yet scientists have been unable to duplicate the processes that marine mussels use to create adhesive structures. This study provides a background on adhesive proteins identified in the blue mussel, Mytilus edulis, and introduces our research interests and discusses the future for continued research related to mussel adhesion.

  6. GABA-BZD Receptor Modulating Mechanism of Panax quinquefolius against 72-hours Sleep Deprivation Induced Anxiety like Behavior: Possible Roles of Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation

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    Priyanka eChanana

    2016-03-01

    Full Text Available ABSTRACTRationale- Panax quinquefolius (American Ginseng is known for its therapeutic potential against various neurological disorders, but its plausible mechanism of action still remains undeciphered. GABA (Gamma Amino Butyric Acid plays an important role in sleep wake cycle homeostasis. Thus there exists rationale in exploring the GABA-ergic potential of Panax quinquefolius as neuroprotective strategy in sleep deprivation induced secondary neurological problems.Objective- The present study was designed to explore the possible GABA-ergic mechanism in the neuro-protective effect of Panax quinquefolius against 72-hours sleep deprivation induced anxiety like behaviour, oxidative stress, mitochondrial dysfunction, HPA-axis activation and neuroinflammation.Materials and Methods- Male laca mice were sleep deprived for 72-hours by using Grid suspended over water method. Panax quinquefolius (American Ginseng 50, 100 and 200 mg/kg was administered alone and in combination with GABA modulators (GABA Cl- channel inhibitor, GABA-benzodiazepine receptor inhibitor and GABAA agonist for 8 days, starting five days prior to 72-hours sleep deprivation period. Various behavioural (locomotor activity, mirror chamber test, biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels, mitochondrial complexes, neuroinflammation marker (Tumour Necrosis Factor, TNF-alpha, serum corticosterone, and histopathological sections of brains were assessed. Results- 72-hours sleep deprivation significantly impaired locomotor activity, caused anxiety-like behaviour, conditions of oxidative stress, alterations in mitochondrial enzyme complex activities, raised serum corticosterone levels, brain TNFα levels and led to neuroinflammation like signs in discrete brain areas as compared to naive group. Panax quinquefolius (100 and 200 mg/kg treatment restored the behavioural, biochemical, mitochondrial, molecular and histopathological alterations. Pre-treatment of

  7. Enhanced neuroinflammation and pain hypersensitivity after peripheral nerve injury in rats expressing mutated superoxide dismutase 1

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    Lavand'homme Patricia

    2011-04-01

    Full Text Available Abstract Background Neuroinflammation and nitroxidative stress are implicated in the pathophysiology of neuropathic pain. In view of both processes, microglial and astroglial activation in the spinal dorsal horn play a predominant role. The present study investigated the severity of neuropathic pain and the degree of glial activation in an inflammatory- and nitroxidative-prone animal model. Methods Transgenic rats expressing mutated superoxide dismutase 1 (hSOD1G93A are classically used as a model for amyotrophic lateral sclerosis (ALS. Because of the associated inflammatory- and nitroxidative-prone properties, this model was used to study thermal and mechanical hypersensitivity following partial sciatic nerve ligation (PSNL. Next to pain hypersensitivity assessment, microglial and astroglial activation states were moreover characterized, as well as inflammatory marker gene expression and the glutamate clearance system. Results PSNL induced thermal and mechanical hypersensitivity in both wild-type (WT and transgenic rats. However, the degree of thermal hypersensitivity was found to be exacerbated in transgenic rats while mechanical hypersensitivity was only slightly and not significantly increased. Microglial Iba1 expression was found to be increased in the ipsilateral dorsal horn of the lumbar spinal cord after PSNL but such Iba1 up-regulation was enhanced in transgenic rats as compared WT rats, both at 3 days and at 21 days after injury. Moreover, mRNA levels of Nox2, a key enzyme in microglial activation, but also of pro-inflammatory markers (IL-1β and TLR4 were not modified in WT ligated rats at 21 days after PSNL as compared to WT sham group while transgenic ligated rats showed up-regulated gene expression of these 3 targets. On the other hand, the PSNL-induced increase in GFAP immunoreactivity spreading that was evidenced in WT rats was unexpectedly found to be attenuated in transgenic ligated rats. Finally, GLT-1 gene expression and

  8. Quercetin along with piperine prevents cognitive dysfunction, oxidative stress and neuro-inflammation associated with mouse model of chronic unpredictable stress.

    Science.gov (United States)

    Rinwa, Puneet; Kumar, Anil

    2017-10-01

    Stress occurs in everyday life and persistence of it causes memory loss. Bioflavonoids like quercetin are reported to have poor bioavailability and limited therapeutic potential against stress induced neurological disorders. Therefore, the present study is an attempt to elucidate the therapeutic potency of combination of quercetin with piperine; a bioavailability enhancer against chronic unpredictable stress (CUS)-induced behavioral and biochemical alterations. Laca mice were subjected to a series of stressful events for a period of 28 days. Quercetin (20, 40 and 80 mg/kg, p.o.), piperine (20 mg/kg, p.o.) and their combinations were administered daily 30 min before CUS procedure. Piracetam (100 mg/kg, i.p.) served as a standard control. CUS caused impaired spatial navigation in Morris water maze test and poor retention in elevated plus maze task. Further, there was significant increase in brain oxidative stress markers and neuro-inflammation (TNF-α). This was coupled with marked rise in acetylcholinesterase and serum corticosterone levels. Co-administration of piperine with quercetin significantly elevated their potential to restore these behavioral, biochemical and molecular changes associated with mouse model of CUS. These results suggest that piperine enhances the neuroprotective effects of quercetin against CUS-induced oxidative stress, neuro-inflammation and memory deficits.

  9. Chapter 9:Wood Adhesion and Adhesives

    Science.gov (United States)

    Charles R. Frihart

    2013-01-01

    The recorded history of bonding wood dates back at least 3000 years to the Egyptians (Skeist and Miron 1990, River 1994a), and adhesive bonding goes back to early mankind (Keimel 2003). Although wood and paper bonding are the largest applications for adhesives, some of the fundamental aspects leading to good bonds are not fully understood. Better understanding of these...

  10. Infiltrating regulatory B cells control neuroinflammation following viral brain infection.

    Science.gov (United States)

    Mutnal, Manohar B; Hu, Shuxian; Schachtele, Scott J; Lokensgard, James R

    2014-12-15

    Previous studies have demonstrated the existence of a subset of B lymphocytes, regulatory B cells (Bregs), which modulate immune function. In this study, in vivo and in vitro experiments were undertaken to elucidate the role of these Bregs in controlling neuroinflammation following viral brain infection. We used multicolor flow cytometry to phenotype lymphocyte subpopulations infiltrating the brain, along with in vitro cocultures to assess their anti-inflammatory and immunoregulatory roles. This distinctive subset of CD19(+)CD1d(hi)CD5(+) B cells was found to infiltrate the brains of chronically infected animals, reaching highest levels at the latest time point tested (30 d postinfection). B cell-deficient Jh(-/-) mice were found to develop exacerbated neuroimmune responses as measured by enhanced accumulation and/or retention of CD8(+) T cells within the brain, as well as increased levels of microglial activation (MHC class II). Conversely, levels of Foxp3(+) regulatory T cells were found to be significantly lower in Jh(-/-) mice when compared with wild-type (Wt) animals. Further experiments showed that in vitro-generated IL-10-secreting Bregs (B10) were able to inhibit cytokine responses from microglia following stimulation with viral Ags. These in vitro-generated B10 cells were also found to promote proliferation of regulatory T cells in coculture studies. Finally, gain-of-function experiments demonstrated that reconstitution of Wt B cells into Jh(-/-) mice restored neuroimmune responses to levels exhibited by infected Wt mice. Taken together, these results demonstrate that Bregs modulate T lymphocyte as well as microglial cell responses within the infected brain and promote CD4(+)Foxp3(+) T cell proliferation in vitro. Copyright © 2014 by The American Association of Immunologists, Inc.

  11. Inhibition of Neuroinflammation in LPS-Activated Microglia by Cryptolepine

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    Olumayokun A. Olajide

    2013-01-01

    Full Text Available Cryptolepine, an indoloquinoline alkaloid in Cryptolepis sanguinolenta, has anti-inflammatory property. In this study, we aimed to evaluate the effects of cryptolepine on lipopolysaccharide (LPS- induced neuroinflammation in rat microglia and its potential mechanisms. Microglial activation was induced by stimulation with LPS, and the effects of cryptolepine pretreatment on microglial activation and production of proinflammatory mediators, PGE2/COX-2, microsomal prostaglandin E2 synthase and nitric oxide/iNOS were investigated. We further elucidated the role of Nuclear Factor-kappa B (NF-κB and the mitogen-activated protein kinases in the antiinflammatory actions of cryptolepine in LPS-stimulated microglia. Our results showed that cryptolepine significantly inhibited LPS-induced production of tumour necrosis factor-alpha (TNFα, interleukin-6 (IL-6, interleukin-1beta (IL-1β, nitric oxide, and PGE2. Protein and mRNA levels of COX-2 and iNOS were also attenuated by cryptolepine. Further experiments on intracellular signalling mechanisms show that IκB-independent inhibition of NF-κB nuclear translocation contributes to the anti-neuroinflammatory actions of cryptolepine. Results also show that cryptolepine inhibited LPS-induced p38 and MAPKAPK2 phosphorylation in the microglia. Cell viability experiments revealed that cryptolepine (2.5 and 5 μM did not produce cytotoxicity in microglia. Taken together, our results suggest that cryptolepine inhibits LPS-induced microglial inflammation by partial targeting of NF-κB signalling and attenuation of p38/MAPKAPK2.

  12. P-glycoprotein acts as an immunomodulator during neuroinflammation.

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    Gijs Kooij

    Full Text Available BACKGROUND: Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system in which autoreactive myelin-specific T cells cause extensive tissue damage, resulting in neurological deficits. In the disease process, T cells are primed in the periphery by antigen presenting dendritic cells (DCs. DCs are considered to be crucial regulators of specific immune responses and molecules or proteins that regulate DC function are therefore under extensive investigation. We here investigated the potential immunomodulatory capacity of the ATP binding cassette transporter P-glycoprotein (P-gp. P-gp generally drives cellular efflux of a variety of compounds and is thought to be involved in excretion of inflammatory agents from immune cells, like DCs. So far, the immunomodulatory role of these ABC transporters is unknown. METHODS AND FINDINGS: Here we demonstrate that P-gp acts as a key modulator of adaptive immunity during an in vivo model for neuroinflammation. The function of the DC is severely impaired in P-gp knockout mice (Mdr1a/1b-/-, since both DC maturation and T cell stimulatory capacity is significantly decreased. Consequently, Mdr1a/1b -/- mice develop decreased clinical signs of experimental autoimmune encephalomyelitis (EAE, an animal model for multiple sclerosis. Reduced clinical signs coincided with impaired T cell responses and T cell-specific brain inflammation. We here describe the underlying molecular mechanism and demonstrate that P-gp is crucial for the secretion of pro-inflammatory cytokines such as TNF-alpha and IFN-gamma. Importantly, the defect in DC function can be restored by exogenous addition of these cytokines. CONCLUSIONS: Our data demonstrate that P-gp downmodulates DC function through the regulation of pro-inflammatory cytokine secretion, resulting in an impaired immune response. Taken together, our work highlights a new physiological role for P-gp as an immunomodulatory molecule and reveals a possible

  13. Protection of MPTP-induced neuroinflammation and neurodegeneration by Pycnogenol

    Science.gov (United States)

    Khan, Mohammad Moshahid; Kempuraj, Duraisamy; Thangavel, Ramasamy; Zaheer, Asgar

    2013-01-01

    Oxidative stress and inflammation play a crucial role in Parkinson’s disease (PD) pathogenesis and may represent a target for treatment. Current PD drugs provide only symptomatic relief and have limitations in terms of adverse effects and inability to prevent neurodegeneration. Flavonoids have been suggested to exert human health benefits by its anti-oxidant and anti-inflammatory properties. Therefore, in the present study, using 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydro pyridine (MPTP)-induced mouse model of Parkinsonism, we investigated the neuroprotective potential of bioflavonoid compound Pycnogenol® (PYC), an extract of Pinus maritime bark. MPTP injected mice developed significantly severe oxidative stress and impaired motor coordination at day 1 and day 7 postinjection. This was associated with significantly increased inflammatory responses of astrocyte and microglia as assessed by ionized calcium binding adaptor molecule 1 (Iba 1) and glial fibrillary acidic protein (GFAP) immunohistochemistry, and nuclear transcription factor-κB (NF-kB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the striata by Western blot. Additionally, there was significant upregulation of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) expression in the striata of MPTP injected mice compared to saline controls. The MPTP-induced neuroinflammation, neurodegeneration and behavioral impairments were markedly repudiated by treatment with PYC. These results suggest that PYC protects dopaminergic neurons from MPTP toxicity in the mouse model of PD. Thus, the present finding of PYC-induced adaptation to oxidative stress and inflammation could suggest a novel avenue for clinical intervention in neurodegenerative diseases including PD. PMID:23391521

  14. Nuclear imaging of neuroinflammation: a comprehensive review of [{sup 11}C]PK11195 challengers

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, Fabien; Camp, Nadja van; Tavitian, Bertrand [Service Hospitalier Frederic Joliot, Laboratoire d' Imagerie Moleculaire Experimentale, CEA, Institut d' Imagerie BioMedicale, Orsay (France); INSERM, U803, Orsay (France); Boutin, Herve [University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Dolle, Frederic [Service Hospitalier Frederic Joliot, Laboratoire d' Imagerie Moleculaire Experimentale, CEA, Institut d' Imagerie BioMedicale, Orsay (France)

    2008-12-15

    Neurodegenerative, inflammatory and neoplastic brain disorders involve neuroinflammatory reactions, and a biomarker of neuroinflammation would be useful for diagnostic, drug development and therapy control of these frequent diseases. In vivo imaging can document the expression of the peripheral benzodiazepine receptor (PBR)/translocator protein 18 kDa (TSPO) that is linked to microglial activation and considered a hallmark of neuroinflammation. The prototype positron emission tomography tracer for PBR, [{sup 11}C]PK11195, has shown limitations that until now have slowed the clinical applications of PBR imaging. In recent years, dozens of new PET and SPECT radioligands for the PBR have been radiolabelled, and several have been evaluated in imaging protocols. Here we review the new PBR ligands proposed as challengers of [{sup 11}C]PK11195, critically analyze preclinical imaging studies and discuss their potential as neuroinflammation imaging agents. (orig.)

  15. Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches

    Science.gov (United States)

    Llorens-Martín, María; Hernández, Félix; Avila, Jesús

    2013-01-01

    Neuroinflammation, a specialized immune response that takes place in the central nervous system, has been linked to neurodegenerative diseases, and specially, it has been considered as a hallmark of Alzheimer disease, the most common cause of dementia in the elderly nowadays. Furthermore, neuroinflammation has been demonstrated to affect important processes in the brain, such as the formation of new neurons, commonly known as adult neurogenesis. For this, many therapeutic approaches have been developed in order to avoid or mitigate the deleterious effects caused by the chronic activation of the immune response. Considering this, in this paper we revise the relationships between neuroinflammation, Alzheimer disease, and adult neurogenesis, as well as the current therapeutic approaches that have been developed in the field. PMID:23690659

  16. Oridonin attenuates Aβ1-42-induced neuroinflammation and inhibits NF-κB pathway.

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    Sulei Wang

    Full Text Available Neuroinflammation induced by beta-amyloid (Aβ plays a critical role in the pathogenesis of Alzheimer's disease (AD, and inhibiting Aβ-induced neuroinflammation serves as a potential strategy for the treatment of AD. Oridonin (Ori, a compound of Rabdosia rubescens, has been shown to exert anti-inflammatory effects. In this study, we demonstrated that Ori inhibited glial activation and decreased the release of inflammatory cytokines in the hippocampus of Aβ1-42-induced AD mice. In addition, Ori inhibited the NF-κB pathway and Aβ1-42-induced apoptosis. Furthermore, Ori could attenuate memory deficits in Aβ1-42-induced AD mice. In conclusion, our study demonstrated that Ori inhibited the neuroinflammation and attenuated memory deficits induced by Aβ1-42, suggesting that Ori might be a promising candidate for AD treatment.

  17. Paroxetine prevented the down-regulation of astrocytic L-Glu transporters in neuroinflammation.

    Science.gov (United States)

    Fujimori, Koki; Takaki, Junpei; Shigemoto-Mogami, Yukari; Sekino, Yuko; Suzuki, Takeshi; Sato, Kaoru

    2015-01-01

    The extracellular L-glutamate (L-Glu) concentration is elevated in neuroinflammation, thereby causing excitotoxicity. One of the mechanisms is down-regulation of astrocyte L-Glu transporters. Some antidepressants have anti-inflammatory effects. We therefore investigated effects of various antidepressants on the down-regulation of astrocyte L-Glu transporters in the in vitro neuroinflammation model. Among these antidepressants, only paroxetine was effective. We previously demonstrated that the down-regulation of astrocyte L-Glu transporters was caused by L-Glu released from activated microglia. We here clarified that only paroxetine inhibited L-Glu release from microglia. This is the novel action of paroxetine, which may bring advantages on the therapy of neuroinflammation. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.

  18. Paroxetine prevented the down-regulation of astrocytic L-Glu transporters in neuroinflammation

    Directory of Open Access Journals (Sweden)

    Koki Fujimori

    2015-01-01

    Full Text Available The extracellular L-glutamate (L-Glu concentration is elevated in neuroinflammation, thereby causing excitotoxicity. One of the mechanisms is down-regulation of astrocyte L-Glu transporters. Some antidepressants have anti-inflammatory effects. We therefore investigated effects of various antidepressants on the down-regulation of astrocyte L-Glu transporters in the in vitro neuroinflammation model. Among these antidepressants, only paroxetine was effective. We previously demonstrated that the down-regulation of astrocyte L-Glu transporters was caused by L-Glu released from activated microglia. We here clarified that only paroxetine inhibited L-Glu release from microglia. This is the novel action of paroxetine, which may bring advantages on the therapy of neuroinflammation.

  19. PH dependent adhesive peptides

    Science.gov (United States)

    Tomich, John; Iwamoto, Takeo; Shen, Xinchun; Sun, Xiuzhi Susan

    2010-06-29

    A novel peptide adhesive motif is described that requires no receptor or cross-links to achieve maximal adhesive strength. Several peptides with different degrees of adhesive strength have been designed and synthesized using solid phase chemistries. All peptides contain a common hydrophobic core sequence flanked by positively or negatively charged amino acids sequences.

  20. [Neuroinflammation in the Brain of Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome].

    Science.gov (United States)

    Nakatomi, Yasuhito; Kuratsune, Hirohiko; Watanabe, Yasuyoshi

    2018-01-01

    Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by chronic, profound, disabling, and unexplained fatigue; cognitive impairment; and chronic widespread pain. By using positron emission tomography, our study demonstrated neuroinflammation in the brain of patients with ME/CFS. Neuroinflammation was found to be widespread in the brain areas of the patients with ME/CFS and was associated with the severity of their neuropsychological symptoms. The ongoing research would lead to the establishment of objective diagnostic criteria and development of an appropriate therapy.

  1. Marker chromosomes.

    Science.gov (United States)

    Rao, Kiran Prabhaker; Belogolovkin, Victoria

    2013-04-01

    Marker chromosomes are a morphologically heterogeneous group of structurally abnormal chromosomes that pose a significant challenge in prenatal diagnosis. Phenotypes associated with marker chromosomes are highly variable and range from normal to severely abnormal. Clinical outcomes are very difficult to predict when marker chromosomes are detected prenatally. In this review, we outline the classification, etiology, cytogenetic characterization, and clinical consequences of marker chromosomes, as well as practical approaches to prenatal diagnosis and genetic counseling.

  2. Particle adhesion and removal

    CERN Document Server

    Mittal, K L

    2015-01-01

    The book provides a comprehensive and easily accessible reference source covering all important aspects of particle adhesion and removal.  The core objective is to cover both fundamental and applied aspects of particle adhesion and removal with emphasis on recent developments.  Among the topics to be covered include: 1. Fundamentals of surface forces in particle adhesion and removal.2. Mechanisms of particle adhesion and removal.3. Experimental methods (e.g. AFM, SFA,SFM,IFM, etc.) to understand  particle-particle and particle-substrate interactions.4. Mechanics of adhesion of micro- and  n

  3. Peripheral Administration of Tumor Necrosis Factor-Alpha Induces Neuroinflammation and Sickness but Not Depressive-Like Behavior in Mice

    Directory of Open Access Journals (Sweden)

    Steven Biesmans

    2015-01-01

    Full Text Available Clinical observations indicate that activation of the TNF-α system may contribute to the development of inflammation-associated depression. Here, we tested the hypothesis that systemic upregulation of TNF-α induces neuroinflammation and behavioral changes relevant to depression. We report that a single intraperitoneal injection of TNF-α in mice increased serum and brain levels of the proinflammatory mediators TNF-α, IL-6, and MCP-1, in a dose- and time-dependent manner, but not IL-1β. Protein levels of the anti-inflammatory cytokine IL-10 increased in serum but not in the brain. The transient release of immune molecules was followed by glial cell activation as indicated by increased astrocyte activation in bioluminescent Gfap-luc mice and elevated immunoreactivity against the microglial marker Iba1 in the dentate gyrus of TNF-α-challenged mice. Additionally, TNF-α-injected mice were evaluated in a panel of behavioral tests commonly used to study sickness and depressive-like behavior in rodents. Our behavioral data imply that systemic administration of TNF-α induces a strong sickness response characterized by reduced locomotor activity, decreased fluid intake, and body weight loss. Depressive-like behavior could not be separated from sickness at any of the time points studied. Together, these results demonstrate that peripheral TNF-α affects the central nervous system at a neuroimmune and behavioral level.

  4. Impact of static cold storage VS hypothermic machine preservation on ischemic kidney graft: inflammatory cytokines and adhesion molecules as markers of ischemia/reperfusion tissue damage. Our preliminary results.

    Science.gov (United States)

    Tozzi, Matteo; Franchin, Marco; Soldini, Gabriele; Ietto, Giuseppe; Chiappa, Corrado; Maritan, Emanuele; Villa, Francesca; Carcano, Giulio; Dionigi, Renzo

    2013-01-01

    At the present time, deceased heart-beating donor kidney allografts are usually stored cold. Extended-criteria donor (ECD) grafts show higher sensitivity to ischemia-reperfusion damage than standard kidneys. The increasing use of marginal organs in clinical transplantation urgently requires a more effective preservation system. Pulsatile hypothermic machine perfusion has shown major advantages over static cold storage in terms of reduced organ injury during preservation and improved early graft function. This preliminary study aims to compare pulsatile hypothermic machine perfusion and static cold storage of kidney allografts, outlining differences in the levels of early inflammatory cytokines (TNF-α, IL-2 and IL-1β) and soluble intracellular adhesion molecule (sICAM-1) in perfusion and preservation liquid. Copyright © 2013 Elsevier Ltd and Surgical Associates Ltd. All rights reserved.

  5. Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Börnsen, Lars Svend; Budtz-Jorgensen, Esben

    2016-01-01

    Objective: To investigate CSF biomarkers of neuroinflammation and neurodegeneration in Huntington disease (HD) gene-expansion carriers compared to controls and to investigate these biomarkers in association with clinical HD rating scales and disease burden score. Methods: We collected CSF from 32...

  6. Neuroinflammation in bipolar disorder : A [C-11]-(R)-PK11195 positron emission tomography study

    NARCIS (Netherlands)

    Haarman, Bartholomeus C.M.; Riemersma -van der Lek, Rixt; de Groot, Jan Cees; Ruhe, Eric; Klein, Hans C; Zandstra, Tjitske E; Burger, Huibert; Schoevers, Robert A.; de Vries, Erik F.J.; Drexhage, Hemmo A; Nolen, Willem A.; Doorduin, Janine

    Background: The "monocyte-T-cell theory of mood disorders" regards neuroinflammation, i.e. marked activation of microglia, as a driving force in bipolar disorder. Microglia activation can be visualized in vivo using [C-11]-(R)-PK11195 PET. Indirect evidence suggests the hippocampus as a potential

  7. Selected CSF biomarkers indicate no evidence of early neuroinflammation in Huntington disease

    DEFF Research Database (Denmark)

    Vinther-Jensen, Tua; Börnsen, Lars Svend; Budtz-Jorgensen, Esben

    2016-01-01

    was the only biomarker that increased in premanifest stages and no evidence of early involvement of neuroinflammation in HD was found. However, we found that the biomarkers for neurodegeneration, MBP and tau, increased during the disease course in manifest HD gene-expansion carriers and were associated...

  8. Novel targets for positron emission tomography (PET) radiopharmaceutical tracers for visualization of neuroinflammation

    Science.gov (United States)

    Shchepetkin, I.; Shvedova, M.; Anfinogenova, Y.; Litvak, M.; Atochin, D.

    2017-08-01

    Non-invasive molecular imaging techniques can enhance diagnosis of neurological diseases to achieve their successful treatment. Positron emission tomography (PET) imaging can identify activated microglia and provide detailed functional information based on molecular biology. This imaging modality is based on detection of isotope labeled tracers, which emit positrons. The review summarizes the developments of various radiolabeled ligands for PET imaging of neuroinflammation.

  9. Magnesium sulfate treatment reverses seizure susceptibility and decreases neuroinflammation in a rat model of severe preeclampsia.

    Directory of Open Access Journals (Sweden)

    Abbie Chapman Johnson

    Full Text Available Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO4 is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB disruption and neuroinflammation that lowers seizure threshold. Further, MgSO4 decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP was combined with a high cholesterol diet (HC to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg required to elicit seizure in RUPP + HC ± MgSO4 and compared to normal pregnant controls (n = 6/group; gestational day 20. RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼ 65% lower vs. control (12.4 ± 1.7 vs. 36.7 ± 3.9 mg/kg PTZ; p<0.05 that was reversed by MgSO4 (45.7 ± 8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC. BBB permeability to sodium fluorescein, measured in-vivo (n = 5-7/group, was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9 ± 1.0 vs. 12.2 ± 0.3 counts/gram ×1000; p<0.05 and was unaffected by MgSO4 (15.6 ± 1.0 counts/gram ×1000; p<0.05 vs. controls. In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35 ± 2% of microglia being active compared to 9 ± 2% in normal pregnancy (p<0.01; n = 3-8/group. MgSO4 treatment reversed neuroinflammation, reducing microglial activation to 6 ± 2% (p<0.01 vs. RUPP+HC. Overall, RUPP+HC rats were in a state of augmented

  10. Reducing Peripheral Inflammation with Infliximab Reduces Neuroinflammation and Improves Cognition in Rats with Hepatic Encephalopathy

    Science.gov (United States)

    Dadsetan, Sherry; Balzano, Tiziano; Forteza, Jerónimo; Cabrera-Pastor, Andrea; Taoro-Gonzalez, Lucas; Hernandez-Rabaza, Vicente; Gil-Perotín, Sara; Cubas-Núñez, Laura; García-Verdugo, José-Manuel; Agusti, Ana; Llansola, Marta; Felipo, Vicente

    2016-01-01

    Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in rats with HE: (1) peripheral inflammation is a main contributor to neuroinflammation; (2) neuroinflammation in hippocampus impairs spatial learning by altering AMPA and/or NMDA receptors membrane expression; (3) reducing peripheral inflammation with infliximab (anti-TNF-a) would improve spatial learning; (4) this would be associated with reduced neuroinflammation and normalization of the membrane expression of glutamate receptors. The aims of this work were to assess these hypotheses. We analyzed in rats with portacaval shunt (PCS) and control rats, treated or not with infliximab: (a) peripheral inflammation by measuring prostaglandin E2, IL10, IL-17, and IL-6; (b) neuroinflammation in hippocampus by analyzing microglial activation and the content of TNF-a and IL-1b; (c) AMPA and NMDA receptors membrane expression in hippocampus; and (d) spatial learning in the Radial and Morris water mazes. We assessed the effects of treatment with infliximab on peripheral inflammation, on neuroinflammation and AMPA and NMDA receptors membrane expression in hippocampus and on spatial learning and memory. PCS rats show increased serum prostaglandin E2, IL-17, and IL-6 and reduced IL-10 levels, indicating increased peripheral inflammation. PCS rats also show microglial activation and increased nuclear NF-kB and expression of TNF-a and IL-1b in hippocampus. This was associated with altered AMPA and NMDA receptors membrane expression in hippocampus and impaired spatial learning and memory in the radial and Morris water maze. Treatment with infliximab reduces peripheral inflammation in PCS rats, normalizing prostaglandin E2, IL-17, IL-6, and

  11. Features of Microglia and Neuroinflammation Relevant to Environmental Exposure and Neurotoxicity

    Directory of Open Access Journals (Sweden)

    G. Jean Harry

    2011-07-01

    Full Text Available Microglia are resident cells of the brain involved in regulatory processes critical for development, maintenance of the neural environment, injury and repair. They belong to the monocytic-macrophage lineage and serve as brain immune cells to orchestrate innate immune responses; however, they are distinct from other tissue macrophages due to their relatively quiescent phenotype and tight regulation by the CNS microenvironment. Microglia actively survey the surrounding parenchyma and respond rapidly to changes such that any disruption to neural architecture or function can contribute to the loss in regulation of the microglia phenotype. In many models of neurodegeneration and neurotoxicity, early events of synaptic degeneration and neuronal loss are accompanied by an inflammatory response including activation of microglia, perivascular monocytes, and recruitment of leukocytes. In culture, microglia have been shown to be capable of releasing several potentially cytotoxic substances, such as reactive oxygen intermediates, nitric oxide, proteases, arachidonic acid derivatives, excitatory amino acids, and cytokines; however, they also produce various neurotrophic factors and quench damage from free radicals and excitotoxins. As the primary source for pro-inflammatory cytokines, microglia are implicated as pivotal mediators of neuroinflammation and can induce or modulate a broad spectrum of cellular responses. Neuroinflammation should be considered as a balanced network of processes whereby subtle modifications can shift the cells toward disparate outcomes. For any evaluation of neuroinflammation and microglial responses, within the framework of neurotoxicity or degeneration, one key question in determining the consequence of neuroinflammation is whether the response is an initiating event or the consequence of tissue damage. As examples of environmental exposure-related neuroinflammation in the literature, we provide an evaluation of data on manganese

  12. The adhesive strength and initial viscosity of denture adhesives.

    Science.gov (United States)

    Han, Jian-Min; Hong, Guang; Dilinuer, Maimaitishawuti; Lin, Hong; Zheng, Gang; Wang, Xin-Zhi; Sasaki, Keiichi

    2014-11-01

    To examine the initial viscosity and adhesive strength of modern denture adhesives in vitro. Three cream-type denture adhesives (Poligrip S, Corect Cream, Liodent Cream; PGS, CRC, LDC) and three powder-type denture adhesives (Poligrip Powder, New Faston, Zanfton; PGP, FSN, ZFN) were used in this study. The initial viscosity was measured using a controlled-stress rheometer. The adhesive strength was measured according to ISO-10873 recommended procedures. All data were analyzed independently by one-way analysis of variance combined with a Student-Newman-Keuls multiple comparison test at a 5% level of significance. The initial viscosity of all the cream-type denture adhesives was lower than the powder-type adhesives. Before immersion in water, all the powder-type adhesives exhibited higher adhesive strength than the cream-type adhesives. However, the adhesive strength of cream-type denture adhesives increased significantly and exceeded the powder-type denture adhesives after immersion in water. For powder-type adhesives, the adhesive strength significantly decreased after immersion in water for 60 min, while the adhesive strength of the cream-type adhesives significantly decreased after immersion in water for 180 min. Cream-type denture adhesives have lower initial viscosity and higher adhesive strength than powder type adhesives, which may offer better manipulation properties and greater efficacy during application.

  13. [Adhesion molecules and cancer].

    Science.gov (United States)

    Pierres, A; Benoliel, A M; Bongrand, P

    1999-12-01

    This review was aimed at summarizing recent advances in the understanding of cell adhesion in order to discuss the possible relevance of new knowledge to the exploration of cancer patients and elaboration of therapeutic strategies. During the last 10 years, many adhesion molecules were identified, thus allowing to determine their tissue distribution and functional regulation. The concept of adhesiveness was refined. It is now well known that adhesive rate (i.e., the minimal contact time required for bond formation) and binding strength (i.e., the minimal force required to detach bound cells) are distinct parameters. They may be regulated independently, and influence the cell behavior in different ways. It is now possible to achieve accurate control of tumor cell adhesiveness, either by inhibiting an adhesive mechanism (through monoclonal antibodies, competitive ligands, or inhibition of receptor expression with antisense strategy or gene knock-out) or by promoting a binding mechanism (with receptor transfection or pro-inflammatory stimulation). Recent progress opens new possibilities for diagnosis and treatment. First, the interpretation of experimental data may be improved. Cell adhesive behavior is not entirely accounted for by the density of membrane adhesion receptors. Indeed, adhesion is influenced by receptor connection to the cytoskeleton and structure of the cell coat. An adhesion receptor may be anti-metastatic through an increase in tumor cohesion and cell differentiation, or pro-metastatic, through facilitation of cell migration towards a target tissue. New therapeutic strategies may include anti-adhesive procedure aimed at preventing metastasis formation. The potential importance of a better control of inflammatory processes is also emphasized in view of the influence of these processes on the expression of adhesion molecules.

  14. Reversible Thermoset Adhesives

    Science.gov (United States)

    Mac Murray, Benjamin C. (Inventor); Tong, Tat H. (Inventor); Hreha, Richard D. (Inventor)

    2016-01-01

    Embodiments of a reversible thermoset adhesive formed by incorporating thermally-reversible cross-linking units and a method for making the reversible thermoset adhesive are provided. One approach to formulating reversible thermoset adhesives includes incorporating dienes, such as furans, and dienophiles, such as maleimides, into a polymer network as reversible covalent cross-links using Diels Alder cross-link formation between the diene and dienophile. The chemical components may be selected based on their compatibility with adhesive chemistry as well as their ability to undergo controlled, reversible cross-linking chemistry.

  15. Adhesion at metal interfaces

    Science.gov (United States)

    Banerjea, Amitava; Ferrante, John; Smith, John R.

    1991-01-01

    A basic adhesion process is defined, the theory of the properties influencing metallic adhesion is outlined, and theoretical approaches to the interface problem are presented, with emphasis on first-principle calculations as well as jellium-model calculations. The computation of the energies of adhesion as a function of the interfacial separation is performed; fully three-dimensional calculations are presented, and universality in the shapes of the binding energy curves is considered. An embedded-atom method and equivalent-crystal theory are covered in the framework of issues involved in practical adhesion.

  16. Gecko adhesion: evolutionary nanotechnology.

    Science.gov (United States)

    Autumn, Kellar; Gravish, Nick

    2008-05-13

    If geckos had not evolved, it is possible that humans would never have invented adhesive nanostructures. Geckos use millions of adhesive setae on their toes to climb vertical surfaces at speeds of over 1ms-1. Climbing presents a significant challenge for an adhesive in requiring both strong attachment and easy rapid removal. Conventional pressure-sensitive adhesives (PSAs) are either strong and difficult to remove (e.g. duct tape) or weak and easy to remove (e.g. sticky notes). The gecko adhesive differs dramatically from conventional adhesives. Conventional PSAs are soft viscoelastic polymers that degrade, foul, self-adhere and attach accidentally to inappropriate surfaces. In contrast, gecko toes bear angled arrays of branched, hair-like setae formed from stiff, hydrophobic keratin that act as a bed of angled springs with similar effective elastic modulus to that of PSAs. Setae are self-cleaning and maintain function for months during repeated use in dirty conditions. Setae are an anisotropic 'frictional adhesive' in that adhesion requires maintenance of a proximally directed shear load, enabling either a tough bond or spontaneous detachment. Gecko-like synthetic adhesives may become the glue of the future-and perhaps the screw of the future as well.

  17. Volume, metabolites and neuroinflammation of the hippocampus in bipolar disorder - A combined magnetic resonance imaging and positron emission tomography study

    NARCIS (Netherlands)

    Haarman, Bartholomeus C. M. ('Benno'); Burger, Huibert; Doorduin, Janine; Renken, Remco J.; Sibeijn-Kuiper, Anita J.; Marsman, Jan-Bernard C.; Vries, de Erik; de Groot, Jan Cees; Drexhage, Hemmo A.; Mendes, Richard; Nolen, Willem A.; Riemersma-Van der Lek, Rixt F.

    Background: The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in

  18. Adhesive compositions and methods

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Scott D.; Sendijarevic, Vahid; O' Connor, James

    2017-12-05

    The present invention encompasses polyurethane adhesive compositions comprising aliphatic polycarbonate chains. In one aspect, the present invention encompasses polyurethane adhesives derived from aliphatic polycarbonate polyols and polyisocyanates wherein the polyol chains contain a primary repeating unit having a structure:. In another aspect, the invention provides articles comprising the inventive polyurethane compositions as well as methods of making such compositions.

  19. adhesive intestinal obstruction

    African Journals Online (AJOL)

    2006-06-01

    Jun 1, 2006 ... ABSTRACT. Background: Adhesions after abdominal and pelvic surgery are a major cause of intestinal obstruction in the western world and the pathology is steadily gaining prominence in our practice. Objective: To determine the magnitude of adhesive intestinal obstruction; to determine the types.

  20. Functionally Graded Adhesives

    Science.gov (United States)

    2009-11-01

    commonly used fillers (6). Titanium dioxide is used to add pigment to an adhesive (7). Fumed silica is employed as a rheology modifier (8). The goal of...provide pigment , increase volume, lower cost, modify 2 strength, and alter adhesive properties (3). Calcium carbonate and talc are inexpensive

  1. Soy protein adhesives

    Science.gov (United States)

    Charles R. Frihart

    2010-01-01

    In the quest to manufacture and use building materials that are more environmentally friendly, soy adhesives can be an important component. Trees fix and store carbon dioxide in the atmosphere. After the trees are harvested, machinery converts the wood into strands, which are then bonded together with adhesives to form strandboard, used in constructing long-lasting...

  2. Carbohydrate mediated bacterial adhesion.

    Science.gov (United States)

    Pieters, Roland J

    2011-01-01

    In the process of adhesion, bacteria often carry proteins on their surface, adhesins, that bind to specific components of tissue cells or the extracellular matrix. In many cases these components are carbohydrate structures. The carbohydrate binding specificities of many bacteria have been uncovered over the years. The design and synthesis of inhibitors of bacterial adhesion has the potential to create new therapeutics for the prevention and possibly treatment of bacterial infections. Unfortunately, the carbohydrate structures often bind only weakly to the adhesion proteins, although drug design approaches can improve the situation. Furthermore, in some cases linking carbohydrates covalently together, to create so-called multivalent systems, can also significantly enhance the inhibitory potency. Besides adhesion inhibition as a potential therapeutic strategy, the adhesion proteins can also be used for detection. Novel methods to do this are being developed. These include the use of microarrays and glyconanoparticles. New developments in these areas are discussed.

  3. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach...... that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation....... As such, adhesion represents the Achilles heel of crucial pathogenic functions. It follows that interference with adhesion can reduce bacterial virulence. Here, we illustrate this important topic with examples of techniques being developed that can inhibit bacterial adhesion. Some of these will become...

  4. Biophysics of cadherin adhesion.

    Science.gov (United States)

    Leckband, Deborah; Sivasankar, Sanjeevi

    2012-01-01

    Since the identification of cadherins and the publication of the first crystal structures, the mechanism of cadherin adhesion, and the underlying structural basis have been studied with a number of different experimental techniques, different classical cadherin subtypes, and cadherin fragments. Earlier studies based on biophysical measurements and structure determinations resulted in seemingly contradictory findings regarding cadherin adhesion. However, recent experimental data increasingly reveal parallels between structures, solution binding data, and adhesion-based biophysical measurements that are beginning to both reconcile apparent differences and generate a more comprehensive model of cadherin-mediated cell adhesion. This chapter summarizes the functional, structural, and biophysical findings relevant to cadherin junction assembly and adhesion. We emphasize emerging parallels between findings obtained with different experimental approaches. Although none of the current models accounts for all of the available experimental and structural data, this chapter discusses possible origins of apparent discrepancies, highlights remaining gaps in current knowledge, and proposes challenges for further study.

  5. Highly Selective Cyclooxygenase-1 Inhibitors P6 and Mofezolac Counteract Inflammatory State both In Vitro and In Vivo Models of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Rosa Calvello

    2017-06-01

    Full Text Available Activated microglia secrete an array of pro-inflammatory factors, such as prostaglandins, whose accumulation contributes to neuronal damages. Prostaglandin endoperoxide synthases or cyclooxygenases (COX-1 and COX-2, which play a critical role in the inflammation, are the pharmacological targets of non-steroidal anti-inflammatory drugs, used to treat pain and inflammation. Since it was reported that COX-1 is the major player in mediating the brain inflammatory response, the aim of this study was to evaluate the effects of highly selective COX-1 inhibitors, such as P6 and mofezolac, in neuroinflammation models. Lipopolysaccharide (LPS-activated mouse BV-2 microglial cells and LPS intracerebroventricular-injected mice as in vitro and in vivo neuroinflammation models, respectively, were used to probe the antiinflammatory efficacy of P6 and mofezolac. Both P6 and mofezolac reduce COX-1 expression in LPS-activated BV-2 cells. This reduction was accompanied with PGE2 release reduction and NF-kB activation downregulation. Coextensively, in the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE2 release and Ikβα phosphorylation amount assayed in the brain areas tested. These results indicate the capability of P6 and mofezolac to modulate the NF-kB signaling pathway, emphasizing the neuroprotective effect and therapeutic potential of COX-1 inhibitors in the control of neuroinflammatory diseases.

  6. (SSR) markers

    African Journals Online (AJOL)

    uwerhiavwe

    Variability was observed for six ... rapid increase in climate change, so there is need to develop high yielding ... the past decade including assessment of genetic diversity in maize ... The SSR gel images and marker data were processed using.

  7. Role of Redox Signaling in Neuroinflammation and Neurodegenerative Diseases

    Directory of Open Access Journals (Sweden)

    Hsi-Lung Hsieh

    2013-01-01

    Full Text Available Reactive oxygen species (ROS, a redox signal, are produced by various enzymatic reactions and chemical processes, which are essential for many physiological functions and act as second messengers. However, accumulating evidence has implicated the pathogenesis of several human diseases including neurodegenerative disorders related to increased oxidative stress. Under pathological conditions, increasing ROS production can regulate the expression of diverse inflammatory mediators during brain injury. Elevated levels of several proinflammatory factors including cytokines, peptides, pathogenic structures, and peroxidants in the central nervous system (CNS have been detected in patients with neurodegenerative diseases such as Alzheimer’s disease (AD. These proinflammatory factors act as potent stimuli in brain inflammation through upregulation of diverse inflammatory genes, including matrix metalloproteinases (MMPs, cytosolic phospholipase A2 (cPLA2, cyclooxygenase-2 (COX-2, and adhesion molecules. To date, the intracellular signaling mechanisms underlying the expression of target proteins regulated by these factors are elusive. In this review, we discuss the mechanisms underlying the intracellular signaling pathways, especially ROS, involved in the expression of several inflammatory proteins induced by proinflammatory factors in brain resident cells. Understanding redox signaling transduction mechanisms involved in the expression of target proteins and genes may provide useful therapeutic strategies for brain injury, inflammation, and neurodegenerative diseases.

  8. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression

    Directory of Open Access Journals (Sweden)

    Ru-Yin Tsai

    2016-06-01

    Conclusion: Resveratrol restores the antinociceptive effect of morphine by reversing morphine infusion-induced spinal cord neuroinflammation and increase in TNFR1 expression. The reversal of the morphine-induced increase in TNFR1 expression by resveratrol is partially due to reversal of the morphine infusion-induced increase in HDAC1 expression. Resveratrol pretreatment can be used as an adjuvant in clinical pain management for patients who need long-term morphine treatment or with neuropathic pain.

  9. Inflammasomes in neuroinflammation and changes in brain function: a focused review

    Directory of Open Access Journals (Sweden)

    Gaurav eSinghal

    2014-10-01

    Full Text Available Recent literature has pointed to the existence of inflammasome-mediated inflammatory pathways in central nervous system disorders and associated changes in behavior. Neuroinflammation, which is an innate immune response in the central nervous system against harmful and irritable stimuli such as pathogens and metabolic toxic waste, as well as to chronic mild stress, is mediated by protein complexes known as inflammasomes. Inflammasomes activate pro-inflammatory caspases 1 and 5, which then cleave the precursor forms of pro-inflammatory cytokines IL-1β, IL-18 and IL-33 into their active forms. These pro-inflammatory cytokines have been shown to promote a variety of innate immune processes associated with infection, inflammation and autoimmunity, and thereby play an instrumental role in the instigation of neuroinflammation during old age and subsequent occurrence of neurodegenerative diseases, cognitive impairment and dementia. In particular, NLRP inflammasomes may also have a role in the etiologies of depression, Alzheimer’s disease and in metabolic disorders, such as Type II diabetes, obesity and cardiovascular diseases that have been shown to be co-morbid with psychiatric illnesses. It has been reported that while these inflammasomes may be activated through TNF-α dependent pathways, other cytokines, like IFN-γ, may assist in inhibiting their activation and thus delay disease progression. Furthermore some other cytokines, including IL-6, may not have a direct role in inflammasome-mediated diseases. An array of recent research suggests that NLRP inflammasomes targeted therapies could be used for alleviating neuroinflammation and for treatment of associated psychiatric illnesses, although this still remains a challenge and necessitates further extensive research. This review examines the complex inflammatory signaling pathways involved in the activation of NLRP inflammasomes and the role they play in promoting neuroinflammation and subsequent

  10. Neuroinflammation and Depression: Microglia Activation, Extracellular Microvesicles and microRNA Dysregulation

    OpenAIRE

    Brites, Dora; Fernandes, Adelaide

    2015-01-01

    Patients with chronic inflammation are often associated with the emergence of depression symptoms, while diagnosed depressed patients show increased levels of circulating cytokines. Further studies revealed the activation of the brain immune cell microglia in depressed patients with a greater magnitude in individuals that committed suicide, indicating a crucial role for neuroinflammation in depression brain pathogenesis. Rapid advances in the understanding of microglial and astrocytic neurobi...

  11. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation

    OpenAIRE

    Dora eBrites; Adelaide eFernandes

    2015-01-01

    Patients with chronic inflammation are often associated with the emergence of depression symptoms, while diagnosed depressed patients show increased levels of circulating cytokines. Further studies revealed the activation of the brain immune cell microglia in depressed patients with a greater magnitude in individuals that committed suicide, indicating a crucial role for neuroinflammation in depression brain pathogenesis. Rapid advances in the understanding of microglial and astrocytic neurobi...

  12. Mussel adhesion - essential footwork.

    Science.gov (United States)

    Waite, J Herbert

    2017-02-15

    Robust adhesion to wet, salt-encrusted, corroded and slimy surfaces has been an essential adaptation in the life histories of sessile marine organisms for hundreds of millions of years, but it remains a major impasse for technology. Mussel adhesion has served as one of many model systems providing a fundamental understanding of what is required for attachment to wet surfaces. Most polymer engineers have focused on the use of 3,4-dihydroxyphenyl-l-alanine (Dopa), a peculiar but abundant catecholic amino acid in mussel adhesive proteins. The premise of this Review is that although Dopa does have the potential for diverse cohesive and adhesive interactions, these will be difficult to achieve in synthetic homologs without a deeper knowledge of mussel biology; that is, how, at different length and time scales, mussels regulate the reactivity of their adhesive proteins. To deposit adhesive proteins onto target surfaces, the mussel foot creates an insulated reaction chamber with extreme reaction conditions such as low pH, low ionic strength and high reducing poise. These conditions enable adhesive proteins to undergo controlled fluid-fluid phase separation, surface adsorption and spreading, microstructure formation and, finally, solidification. © 2017. Published by The Company of Biologists Ltd.

  13. Alginate-Derived Oligosaccharide Inhibits Neuroinflammation and Promotes Microglial Phagocytosis of β-Amyloid

    Directory of Open Access Journals (Sweden)

    Rui Zhou

    2015-09-01

    Full Text Available Alginate from marine brown algae has been widely applied in biotechnology. In this work, the effects of alginate-derived oligosaccharide (AdO on lipopolysaccharide (LPS/β-amyloid (Aβ-induced neuroinflammation and microglial phagocytosis of Aβ were studied. We found that pretreatment of BV2 microglia with AdO prior to LPS/Aβ stimulation led to a significant inhibition of production of nitric oxide (NO and prostaglandin E2 (PGE2, expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 and secretion of proinflammatory cytokines. We further demonstrated that AdO remarkably attenuated the LPS-activated overexpression of toll-like receptor 4 (TLR4 and nuclear factor (NF-κB in BV2 cells. In addition to the impressive inhibitory effect on neuroinflammation, we also found that AdO promoted the phagocytosis of Aβ through its interaction with TLR4 in microglia. Our results suggested that AdO exerted the inhibitory effect on neuroinflammation and the promotion effect on microglial phagocytosis, indicating its potential as a nutraceutical or therapeutic agent for neurodegenerative diseases, particularly Alzheimer’s disease (AD.

  14. Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

    Science.gov (United States)

    Foucault-Fruchard, Laura; Antier, Daniel

    2017-01-01

    Neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's diseases, are all characterized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist. PMID:29089979

  15. Neuroinflammation and neurosteroidogenesis: Reciprocal modulation during injury to the adult zebra finch brain.

    Science.gov (United States)

    Pedersen, Alyssa L; Brownrout, Jenna L; Saldanha, Colin J

    2017-10-13

    Estrogens like estradiol (E 2 ) via their receptors are pluripotent steroid hormones that exert a profound influence on the developing and adult brain in many vertebrates. In songbirds and mammals, acute brain injury resulting from mechanical damage, anoxia and ischemia rapidly upregulates aromatase and E 2 synthesis. Interestingly, this E 2 provision occurs due to the induction of aromatase expression in reactive astrocytes in areas surrounding brain injury. The resultant increase in E 2 is neuroprotective with established influences on apoptosis, gliosis, cytogenesis, neurogenesis and neuroinflammation. Correspondingly, E 2 decreases secondary damage following acute brain trauma and may improve recovery. Until very recently however, the signals responsible for the induction of astrocytic aromatase expression in reactive astrocytes were unknown. In the current review, we discuss what is known about the role of astrocytic E 2 in neuroprotection with a particular emphasis on a recently discovered interaction between neuroinflammatory and steroidogenic signaling in the zebra finch. We first describe the role of acute inflammatory signaling in the regulation of astrocytic aromatase and central E 2 levels. Next, we discuss the emerging role of central E 2 in the control of chronic neuroinflammation. Finally, we provide a framework for further work investigating the important role of the interaction between inflammatory and steroidogenic signaling in the protection of neural circuits and behavior following traumatic brain injury (TBI). We also highlight dimorphisms that point to important aspects of sex-specific pathways that underlie the interactions of neuroinflammation and neurosteroidogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Hippocampal neurogenesis dysfunction linked to depressive-like behaviors in a neuroinflammation induced model of depression.

    Science.gov (United States)

    Tang, Ming-Ming; Lin, Wen-Juan; Pan, Yu-Qin; Guan, Xi-Ting; Li, Ying-Cong

    2016-07-01

    Our previous work found that triple central lipopolysaccharide (LPS) administration could induce depressive-like behaviors and increased central pro-inflammatory cytokines mRNA, hippocampal cytokine mRNA in particular. Since several neuroinflammation-associated conditions have been reported to impair neurogenesis, in this study, we further investigated whether the neuroinflammation induced depression would be associated with hippocampal neurogenesis dysfunction. An animal model of depression induced by triple central lipopolysaccharide (LPS) administration was used. In the hippocampus, the neuroinflammatory state evoked by LPS was marked by an increased production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α. It was found that rats in the neuroinflammatory state exhibited depressive-like behaviors, including reduced saccharin preference and locomotor activity as well as increased immobility time in the tail suspension test and latency to feed in the novelty suppressed feeding test. Adult hippocampal neurogenesis was concomitantly inhibited, including decreased cell proliferation and newborn cell survival. We also demonstrated that the decreased hippocampal neurogenesis in cell proliferation was significantly correlated with the depressive-like phenotypes of decreased saccharine preference and distance travelled, the core and characteristic symptoms of depression, under neuro inflammation state. These findings provide the first evidence that hippocampal neurogenesis dysfunction is correlated with neuroinflammation-induced depression, which suggests that hippocampal neurogenesis might be one of biological mechanisms underlying depression induced by neruoinflammation. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Laura Foucault-Fruchard

    2017-01-01

    Full Text Available Neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's diseases, are all characterized by a component of innate immunity called neuroinflammation. Neuronal loss and neuroinflammation are two phenomena closely linked. Hence, the neuroinflammation is a relevant target for the management of the neurodegenerative diseases given that, to date, there is no treatment to stop neuronal loss. Several studies have investigated the potential effects of activators of alpha 7 nicotinic acetylcholine receptors in animal models of neurodegenerative diseases. These receptors are widely distributed in the central nervous system. After activation, they seem to mediate the cholinergic anti-inflammatory pathway in the brain. This anti-inflammatory pathway, first described in periphery, regulates activation of microglial cells considered as the resident macrophage population of the central nervous system. In this article, we shortly review the agonists of the alpha 7 nicotinic acetylcholine receptors that have been evaluated in vivo and we focused on the selective positive allosteric modulators of these receptors. These compounds represent a key element to enhance receptor activity only in the presence of the endogenous agonist.

  18. Global and 3D spatial assessment of neuroinflammation in rodent models of Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Shashank Gupta

    Full Text Available Multiple Sclerosis (MS is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS. T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE animal models for the disease. A technology for quantitative and 3 dimensional (3D spatial assessment of inflammation in this and other CNS inflammatory conditions is much needed. Here we present a procedure for 3D spatial assessment and global quantification of the development of neuroinflammation based on Optical Projection Tomography (OPT. Applying this approach to the analysis of rodent models of MS, we provide global quantitative data of the major inflammatory component as a function of the clinical course. Our data demonstrates a strong correlation between the development and progression of neuroinflammation and clinical disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy in animal models of MS and other neuroinflammatory/neurodegenerative disorders.

  19. Handbook of adhesion

    CERN Document Server

    Packham, D E

    2006-01-01

    This second edition of the successful Handbook of Adhesion provides concise and authoritative articles covering many aspects of the science and technology associated with adhesion and adhesives. It is intended to fill a gap between the necessarily simplified treatment of the student textbook and the full and thorough treatment of the research monograph and review article. The articles are structured in such a way, with internal cross-referencing and external literature references, that the reader can build up a broader and deeper understanding, as their needs require.This second edition includ

  20. Effects of sucrose and high fructose corn syrup consumption on spatial memory function and hippocampal neuroinflammation in adolescent rats.

    Science.gov (United States)

    Hsu, Ted M; Konanur, Vaibhav R; Taing, Lilly; Usui, Ryan; Kayser, Brandon D; Goran, Michael I; Kanoski, Scott E

    2015-02-01

    Excessive consumption of added sugars negatively impacts metabolic systems; however, effects on cognitive function are poorly understood. Also unknown is whether negative outcomes associated with consumption of different sugars are exacerbated during critical periods of development (e.g., adolescence). Here we examined the effects of sucrose and high fructose corn syrup-55 (HFCS-55) intake during adolescence or adulthood on cognitive and metabolic outcomes. Adolescent or adult male rats were given 30-day access to chow, water, and either (1) 11% sucrose solution, (2) 11% HFCS-55 solution, or (3) an extra bottle of water (control). In adolescent rats, HFCS-55 intake impaired hippocampal-dependent spatial learning and memory in a Barne's maze, with moderate learning impairment also observed for the sucrose group. The learning and memory impairment is unlikely based on nonspecific behavioral effects as adolescent HFCS-55 consumption did not impact anxiety in the zero maze or performance in a non-spatial response learning task using the same mildly aversive stimuli as the Barne's maze. Protein expression of pro-inflammatory cytokines (interleukin 6, interleukin 1β) was increased in the dorsal hippocampus for the adolescent HFCS-55 group relative to controls with no significant effect in the sucrose group, whereas liver interleukin 1β and plasma insulin levels were elevated for both adolescent-exposed sugar groups. In contrast, intake of HFCS-55 or sucrose in adults did not impact spatial learning, glucose tolerance, anxiety, or neuroinflammatory markers. These data show that consumption of added sugars, particularly HFCS-55, negatively impacts hippocampal function, metabolic outcomes, and neuroinflammation when consumed in excess during the adolescent period of development. © 2014 Wiley Periodicals, Inc.

  1. Adhesion of Lunar Dust

    Science.gov (United States)

    Walton, Otis R.

    2007-01-01

    This paper reviews the physical characteristics of lunar dust and the effects of various fundamental forces acting on dust particles on surfaces in a lunar environment. There are transport forces and adhesion forces after contact. Mechanical forces (i.e., from rover wheels, astronaut boots and rocket engine blast) and static electric effects (from UV photo-ionization and/or tribo-electric charging) are likely to be the major contributors to the transport of dust particles. If fine regolith particles are deposited on a surface, then surface energy-related (e.g., van der Walls) adhesion forces and static-electric-image forces are likely to be the strongest contributors to adhesion. Some measurement techniques are offered to quantify the strength of adhesion forces. And finally some dust removal techniques are discussed.

  2. Bioinspired pressure actuated adhesive system

    NARCIS (Netherlands)

    Paretkar, D.R.; Kamperman, M.M.G.; Schneider, A.S.; Martina, D.; Creton, C.; Arzt, E.

    2011-01-01

    We developed a dry synthetic adhesive system inspired by gecko feet adhesion that can switch reversibly from adhesion to non-adhesion with applied pressure as external stimulus. Micropatterned polydimethylsiloxane (PDMS) surfaces with pillars of 30 µm length and 10 µm diameter were fabricated using

  3. Cohesion and Adhesion with Proteins

    Science.gov (United States)

    Charles R. Frihart

    2016-01-01

    With increasing interest in bio-based adhesives, research on proteins has expanded because historically they have been used by both nature and humans as adhesives. A wide variety of proteins have been used as wood adhesives. Ancient Egyptians most likely used collagens tobond veneer to wood furniture, then came casein (milk), blood, fish scales, and soy adhesives, with...

  4. Prevention of bacterial adhesion

    DEFF Research Database (Denmark)

    Klemm, Per; Vejborg, Rebecca Munk; Hancock, Viktoria

    2010-01-01

    Management of bacterial infections is becoming increasingly difficult due to the emergence and increasing prevalence of bacterial pathogens that are resistant to available antibiotics. Conventional antibiotics generally kill bacteria by interfering with vital cellular functions, an approach...... that imposes selection pressure for resistant bacteria. New approaches are urgently needed. Targeting bacterial virulence functions directly is an attractive alternative. An obvious target is bacterial adhesion. Bacterial adhesion to surfaces is the first step in colonization, invasion, and biofilm formation...

  5. Adhesion on Nanoorganized Multilayers

    Directory of Open Access Journals (Sweden)

    Yolla Kazzi

    2011-01-01

    Full Text Available Nanostructured multilayers composed of alternate organic (alkyldithiol and metallic (gold layers are grafted onto glass plates and prepared in order to modify the mechanical and local dissipative properties of a thin surface layer of the substrate. The adhesion phenomenon between a polyisoprene elastomer and these layers is presented and verified by two theories, namely, Johnson, Kendall, Roberts (JKR and linear elastic fracture mechanics. The increase in adhesion with contact time following a power law has been clearly noted.

  6. Myoferlin depletion elevates focal adhesion kinase and paxillin phosphorylation and enhances cell-matrix adhesion in breast cancer cells.

    Science.gov (United States)

    Blackstone, B N; Li, R; Ackerman, W E; Ghadiali, S N; Powell, H M; Kniss, D A

    2015-04-15

    Breast cancer is the second leading cause of malignant death among women. A crucial feature of metastatic cancers is their propensity to lose adhesion to the underlying basement membrane as they transition to a motile phenotype and invade surrounding tissue. Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins. Focal adhesion kinase (FAK) is pivotal for the organization of focal contacts and maturation into focal adhesions, and disruption of this process is a hallmark of early cancer invasive potential. Our recent work has revealed that myoferlin (MYOF) mediates breast tumor cell motility and invasive phenotype. In this study we demonstrate that noninvasive breast cancer cell lines exhibit increased cell-substrate adhesion and that silencing of MYOF using RNAi in the highly invasive human breast cancer cell line MDA-MB-231 also enhances cell-substrate adhesion. In addition, we detected elevated tyrosine phosphorylation of FAK (FAK(Y397)) and paxillin (PAX(Y118)), markers of focal adhesion protein activation. Morphometric analysis of PAX expression revealed that RNAi-mediated depletion of MYOF resulted in larger, more elongated focal adhesions, in contrast to cells transduced with a control virus (MDA-231(LVC) cells), which exhibited smaller focal contacts. Finally, MYOF silencing in MDA-MB-231 cells exhibited a more elaborate ventral cytoskeletal structure near focal adhesions, typified by pronounced actin stress fibers. These data support the hypothesis that MYOF regulates cell adhesions and cell-substrate adhesion strength and may account for the high degree of motility in invasive breast cancer cells. Copyright © 2015 the American Physiological Society.

  7. Impairment of blood brain barrier is related with the neuroinflammation induced peripheral immune status in intracerebroventricular colchicine injected rats: An experimental study with mannitol.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Arijit; Ghosh, Tusharkanti

    2016-09-01

    The neurodegeneration in AD patients may be associated with changes of peripheral immune responses. Some peripheral immune responses are altered due to neuroinflammation in colchicine induced AD (cAD) rats. The leaky blood brain barrier (BBB) in cAD-rats may be involved in inducing peripheral inflammation, though there is no report in this regard. Therefore, the present study was designed to investigate the role of BBB in cADrats by altering the BBB in a time dependent manner with injection (i.v.) of mannitol (BBB opener). The inflammatory markers in the brain and serum along with the peripheral immune responses were measured after 30 and 60min of mannitol injection in cAD rats. The results showed higher inflammatory markers in the hippocampus and serum along with alterations in peripheral immune parameters in cAD rats. Although the hippocampal inflammatory markers did not further change after mannitol injection in cAD rats, the serum inflammatory markers and peripheral immune responses were altered and these changes were greater after 60min than that of 30min of mannitol injection. The present study shows that the peripheral immune responses in cAD rats after 30 and 60min of mannitol injection are related to magnitude of impairment of BBB in these conditions. It can be concluded from this study that impairment of BBB in cAD rats is related to the changes of peripheral immune responses observed in that condition. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. (SSR) markers

    African Journals Online (AJOL)

    HP-PROBOOK

    2016-10-05

    Oct 5, 2016 ... Cluster analysis was constructed using DARwin program version 6.0. Forty eight (48) coconut individuals were clustered into three groups. Key words: Coconut palm (Cocos nucifera ... markers, cluster analysis, diversity. INTRODUCTION ... industry in Kenya (Muhammed et al., 2013). Furthermore, the slow ...

  9. (SRAP) markers

    African Journals Online (AJOL)

    STORAGESEVER

    2009-06-03

    Jun 3, 2009 ... are a very powerful tool for characterization and genetic diversity estimation. Many molecular marker techniques have been successfully used in identification and genetic diversity analysis in mulberry, such as RAPD (Xiang et al., 1995; Feng et al., 1996; Zhao and Pan, 2004),. AFLP (Sharma and Sharma, ...

  10. (SSR) markers

    African Journals Online (AJOL)

    SAM

    2014-07-30

    Jul 30, 2014 ... and attempt crosses for genetic improvement of the crop. Key words: Capsicum, genetic diversity, molecular characterization, simple sequence repeats (SSR) markers. INTRODUCTION. Chilli pepper (Capsicum annuum L.) (Solanaceae) has a chromosome number 2n=2x=24. It is indigenous to South.

  11. (SSR) markers

    African Journals Online (AJOL)

    Yomi

    2012-04-03

    Apr 3, 2012 ... Oilseed rape (Brassica napus L.) is an important oilseed crop worldwide. The objective of this research was to study the genetic diversity and relationships of B. napus accessions using simple sequence repeat (SSR). A set of 217 genotypes was characterized using 37 SSR markers of mapping on the B.

  12. (RAPD) markers

    African Journals Online (AJOL)

    Administrator

    2011-09-21

    Sep 21, 2011 ... Biotechnol. Biotechnol. Equip.14: 16-18. Belaj A, Satovic Z, Cipriani G, Baldoni L, Testolin R, Rallo L, Trujillo I. (2003). Comparative study of the discriminating capacity of RAPD,. AFLP and SSR markers and of their effectiveness in establishing genetic relationships in olive. Theor. Appl. Genet. 107: 736-744 ...

  13. Intranasal Brain Delivery of Cationic Nanoemulsion-Encapsulated TNFα siRNA in Prevention of Experimental Neuroinflammation

    Science.gov (United States)

    Yadav, Sunita; Gandham, Srujan K.; Panicucci, Riccardo; Amiji, Mansoor M.

    2016-01-01

    Neuroinflammation is a hallmark of acute and chronic neurodegenerative disorders. Activated microglia and secreted factors such as tumor necrosis factor-alpha (TNFα) are key mediators of neuroinflammation and may contribute to neuronal dysfunction. The main aim of this study was to evaluate the therapeutic efficacy of intranasal cationic nanoemulsions encapsulating an anti-TNFα siRNA, for potential anti-inflammatory therapy, tested in an LPS induced model of neuroinflammation. The strategy of developing a cationic nanoemulsion system for silencing the TNFα gene was to efficiently provide neuroprotection against inflammation. TNFα siRNA nanoemulsions were prepared and characterized for particle size, surface charge, morphology, and stability and encapsulation efficiency. Qualitative and quantitative intracellular uptake studies by confocal imaging and flow cytometry, respectively, showed higher uptake compared to Lipofectamine® transfected siRNA. Nanoemulsions showed significantly lower (pnanoemulsions almost 5 fold higher uptake was observed in the rat brain compared to non-encapsulated siRNA. More importantly, intranasal delivery of TNFα siRNA nanoemulsions in vivo markedly reduced the unregulated levels of TNFα in an LPS-induced model of neuroinflammation where TNFα functions as a signaling molecule, which aggravates inflammation. These results indicate that intranasal delivery of cationic nanoemulsions encapsulating TNFα siRNA offered an efficient means of gene knockdown and this approach has significant potential in prevention of neuroinflammation. PMID:26767514

  14. Pycnogenol prevents peritoneal adhesions.

    Science.gov (United States)

    Sahbaz, Ahmet; Aynioglu, Oner; Isik, Hatice; Gun, Banu Dogan; Cengil, Osman; Erol, Onur

    2015-12-01

    This study tested the ability of pycnogenol, an extract from the bark of the French maritime pine (Pinus pinaster), to prevent intra-abdominal adhesions. Thirty female Wistar albino rats were separated randomly into three equal groups: Group (1) the control group, which underwent surgery, but was given no drug; Group (2) given 10 mg/kg of pycnogenol dissolved in normal saline intraperitoneally for 10 days after surgery; and Group (3) given 0.1 mL of normal saline for 10 days intraperitoneally after surgery. On post-operative day 10, all of the animals were killed and any adhesions were evaluated macroscopically and histopathologically. The macroscopic adhesion scores (mean ± SD) for Groups 1, 2, and 3 were 2.5 ± 0.53, 0.60 ± 0.70, and 2.0 ± 0.82, respectively. The macroscopic adhesion score was significantly lower in Group 2 than in Groups 1 and 3 (p Pycnogenol was found to be effective at preventing surgery-related adhesions in an animal model.

  15. Mapping cell surface adhesion by rotation tracking and adhesion footprinting

    Science.gov (United States)

    Li, Isaac T. S.; Ha, Taekjip; Chemla, Yann R.

    2017-03-01

    Rolling adhesion, in which cells passively roll along surfaces under shear flow, is a critical process involved in inflammatory responses and cancer metastasis. Surface adhesion properties regulated by adhesion receptors and membrane tethers are critical in understanding cell rolling behavior. Locally, adhesion molecules are distributed at the tips of membrane tethers. However, how functional adhesion properties are globally distributed on the individual cell’s surface is unknown. Here, we developed a label-free technique to determine the spatial distribution of adhesive properties on rolling cell surfaces. Using dark-field imaging and particle tracking, we extract the rotational motion of individual rolling cells. The rotational information allows us to construct an adhesion map along the contact circumference of a single cell. To complement this approach, we also developed a fluorescent adhesion footprint assay to record the molecular adhesion events from cell rolling. Applying the combination of the two methods on human promyelocytic leukemia cells, our results surprisingly reveal that adhesion is non-uniformly distributed in patches on the cell surfaces. Our label-free adhesion mapping methods are applicable to the variety of cell types that undergo rolling adhesion and provide a quantitative picture of cell surface adhesion at the functional and molecular level.

  16. Cell-matrix adhesion.

    Science.gov (United States)

    Berrier, Allison L; Yamada, Kenneth M

    2007-12-01

    The complex interactions of cells with extracellular matrix (ECM) play crucial roles in mediating and regulating many processes, including cell adhesion, migration, and signaling during morphogenesis, tissue homeostasis, wound healing, and tumorigenesis. Many of these interactions involve transmembrane integrin receptors. Integrins cluster in specific cell-matrix adhesions to provide dynamic links between extracellular and intracellular environments by bi-directional signaling and by organizing the ECM and intracellular cytoskeletal and signaling molecules. This mini review discusses these interconnections, including the roles of matrix properties such as composition, three-dimensionality, and porosity, the bi-directional functions of cellular contractility and matrix rigidity, and cell signaling. The review concludes by speculating on the application of this knowledge of cell-matrix interactions in the formation of cell adhesions, assembly of matrix, migration, and tumorigenesis to potential future therapeutic approaches. 2007 Wiley-Liss, Inc.

  17. Adhesive particle shielding

    Science.gov (United States)

    Klebanoff, Leonard Elliott [Dublin, CA; Rader, Daniel John [Albuquerque, NM; Walton, Christopher [Berkeley, CA; Folta, James [Livermore, CA

    2009-01-06

    An efficient device for capturing fast moving particles has an adhesive particle shield that includes (i) a mounting panel and (ii) a film that is attached to the mounting panel wherein the outer surface of the film has an adhesive coating disposed thereon to capture particles contacting the outer surface. The shield can be employed to maintain a substantially particle free environment such as in photolithographic systems having critical surfaces, such as wafers, masks, and optics and in the tools used to make these components, that are sensitive to particle contamination. The shield can be portable to be positioned in hard-to-reach areas of a photolithography machine. The adhesive particle shield can incorporate cooling means to attract particles via the thermophoresis effect.

  18. The role of immunity and neuroinflammation in genetic predisposition and pathogenesis of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Seoyoung Yoon

    2015-09-01

    Full Text Available Alzheimer's disease is an important public concern with rising prevalence across the globe. While many therapeutic approaches for Alzheimer's disease have been developed, there are currently no validated disease-modifying treatments. Thus, in order to develop novel treatment strategies, there is a significant need to progress our understanding of the pathogenesis of Alzheimer's disease. Several large genome-wide association studies and whole genome and exome sequencing studies have identified novel genes associated with late-onset Alzheimer's disease. Interestingly, many of the genes are associated with inflammation and the immune system, including complement receptor 1, clusterin, CD33, EPH receptor A1, membrane-spanning 4-domains subfamily A, ATP-binding cassette sub-family A member 7, major histocompatibility complex class II, inositol polyphosphate-5-phosphatase, myocyte enhancer factor 2C, and triggering receptor expressed on myeloid cells 2. The pathogenetic contributions of immune reaction and neuroinflammation in Alzheimer's disease have been regarded largely as part of amyloid cascade hypothesis. The neurotoxic amyloid-β (Aβ induces activation of immune cells, such as microglia, astrocytes, perivascular macrophages and lymphocytes and decreased capability of clearing Aβ by immune system and chronic inflammation caused by activated immune cells aggravate neuronal damage and eventually Alzheimer's disease. But the precise mechanism and hereditary impact on such process is largely unknown. The current findings in genetic studies suggest that the immunological mechanisms of Alzheimer's disease may extend beyond passive reaction of Aβ, including the development of Alzheimer's disease such as time of onset and rate of progression. In this article, we aimed to review the mechanisms of immune reaction and neuroinflammation in Alzheimer's disease, with an emphasis on the function of genes known to be associated with a risk of Alzheimer

  19. Scolopendra subspinipes mutilans attenuates neuroinflammation in symptomatic hSOD1G93A mice

    Science.gov (United States)

    2013-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron death in the spinal cord, brainstem, and motor cortex. Neuroinflammation is one of several pathological causes of degenerating motor neurons and is induced by activated microglial cells and astrocytes in ALS. Scolopendra subspinipes mutilans (SSM) is utilized in traditional Chinese and Korean medicine for the treatment of a variety of diseases, such as cancer, apoplexy, and epilepsy. However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity. Methods To determine the effects of SSM on symptomatic hSOD1G93A transgenic mice, SSM (2.5 μℓ/g) was injected bilaterally at the Zusanli (ST36) acupoint three times per week for two weeks. The effects of SSM treatment on anti-neuroinflammation in the brainstem and spinal cord of hSOD1G93A mice were assessed via Nissl and Fluoro-Jade B (FJB) staining, and immunohistochemistry using Iba-1, CD14, HO1, and NQO1 proteins was evaluated by Western blotting. Results In this study, we investigated whether SSM affects neuroinflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes. Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively. Conclusions Our findings suggest that SSM, which has previously been used in complementary and alternative medicine (CAM), might also be considered as an anti-neuroinflammatory therapy for neurodegenerative diseases. PMID:24168240

  20. Scolopendra subspinipes mutilans attenuates neuroinflammation in symptomatic hSOD1(G93A) mice.

    Science.gov (United States)

    Cai, MuDan; Choi, Sun-Mi; Song, Bong Keun; Son, Ilhong; Kim, Sungchul; Yang, Eun Jin

    2013-10-29

    Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron death in the spinal cord, brainstem, and motor cortex. Neuroinflammation is one of several pathological causes of degenerating motor neurons and is induced by activated microglial cells and astrocytes in ALS.Scolopendra subspinipes mutilans (SSM) is utilized in traditional Chinese and Korean medicine for the treatment of a variety of diseases, such as cancer, apoplexy, and epilepsy. However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity. To determine the effects of SSM on symptomatic hSOD1G93A transgenic mice, SSM (2.5 μℓ/g) was injected bilaterally at the Zusanli (ST36) acupoint three times per week for two weeks. The effects of SSM treatment on anti-neuroinflammation in the brainstem and spinal cord of hSOD1G93A mice were assessed via Nissl and Fluoro-Jade B (FJB) staining, and immunohistochemistry using Iba-1, CD14, HO1, and NQO1 proteins was evaluated by Western blotting. In this study, we investigated whether SSM affects neuroinflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes. Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively. Our findings suggest that SSM, which has previously been used in complementary and alternative medicine (CAM), might also be considered as an anti-neuroinflammatory therapy for neurodegenerative diseases.

  1. Annual Research Review: The neuroinflammation hypothesis for stress and psychopathology in children: developmental psychoneuroimmunology

    Science.gov (United States)

    O'Connor, Thomas G.; Moynihan, Jan A.; Caserta, Mary T.

    2014-01-01

    Experimental animal and adult human data suggest that stress exposure is associated with alterations in immune system function that may underlie increased susceptibility to disease and behavioral disorders. The implications of these data for child psychology and psychiatry are not yet clear. The current review seeks to distil and translate the relevant animal and adult human work to children in order to advance a developmental model of psychoneuroimmunology. In addition to reviewing key specific findings, we consider biological/conceptual models and technical aspects of psychoneuroimmunology work in pediatric populations, and outline the rationales and advantages of integrating hypotheses concerning neuroinflammation in developmental studies of psychopathology. PMID:24372371

  2. Mitochondria in neuroinflammation - Multiple sclerosis (MS), leber hereditary optic neuropathy (LHON) and LHON-MS.

    Science.gov (United States)

    Bargiela, David; Chinnery, Patrick F

    2017-06-28

    Mitochondrial dysfunction is associated with neuroinflammation and neurodegenerative disease, but its role as a driver in these processes is uncertain. Understanding the pathogenesis of inherited mitochondrial disorders may help us to uncover mechanisms involved during acquired mitochondrial dysfunction. We review the mechanisms of mitochondrial dysfunction in Leber's hereditary optic neuropathy and multiple sclerosis and discuss shared clinical and molecular features in both conditions. Targeting mitochondrial pathways involved in inflammation or apoptosis may be a possible therapeutic approach in multiple sclerosis. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  3. Periodontitis and Alzheimer's Disease: A Possible Comorbidity between Oral Chronic Inflammatory Condition and Neuroinflammation.

    Science.gov (United States)

    Teixeira, Francisco B; Saito, Miki T; Matheus, Filipe C; Prediger, Rui D; Yamada, Elizabeth S; Maia, Cristiane S F; Lima, Rafael R

    2017-01-01

    Periodontitis is an oral chronic infection/inflammatory condition, identified as a source of mediators of inflammation into the blood circulation, which may contribute to exacerbate several diseases. There is increasing evidence that inflammation plays a key role in the pathophysiology of Alzheimer's disease (AD). Although inflammation is present in both diseases, the exact mechanisms and crosslinks between periodontitis and AD are poorly understood. Therefore, this article aims to review possible comorbidity between periodontitis and AD. Here, the authors discuss the inflammatory aspects of periodontitis, how this oral condition produces a systemic inflammation and, finally, the contribution of this systemic inflammation for worsening neuroinflammation in the progression of AD.

  4. Global and 3D Spatial Assessment of Neuroinflammation in Rodent Models of Multiple Sclerosis

    DEFF Research Database (Denmark)

    Gupta, Shashank; Utoft, Regine Egeholm; Hasseldam, Henrik

    2013-01-01

    Multiple Sclerosis (MS) is a progressive autoimmune inflammatory and demyelinating disease of the central nervous system (CNS). T cells play a key role in the progression of neuroinflammation in MS and also in the experimental autoimmune encephalomyelitis (EAE) animal models for the disease...... disease in several mouse and a rat model of MS refining the information regarding the spatial dynamics of the inflammatory component in EAE. This method provides a powerful tool to investigate the effect of environmental and genetic forces and for assessing the therapeutic effects of drug therapy...

  5. Microglial activation and neuroinflammation in Alzheimer's disease: a critical examination of recent history

    Directory of Open Access Journals (Sweden)

    Wolfgang J Streit

    2010-06-01

    Full Text Available The neurofibrillary degeneration that occurs in Alzheimer’s disease (AD is thought to be the result of a chronic and damaging neuroinflammatory response mediated by neurotoxic substances produced by activated microglial cells. This neuroinflammation hypothesis of AD pathogenesis has led to numerous clinical trials with anti-inflammatory drugs, none of which have shown clear benefits for slowing or preventing disease onset and progression. In this paper, I make the point that AD is not an inflammatory condition, and reconstruct the sequence of events during the 1980s and 1990s that I believe led to the development of this faulty theory.

  6. Cerebrospinal fluid markers of neuroinflammation in delirium: A role for interleukin-1β in delirium after hip fracture

    Science.gov (United States)

    Cape, Eleanor; Hall, Roanna J; van Munster, Barbara C; de Vries, Annick; Howie, Sarah EM; Pearson, Andrew; Middleton, Scott D; Gillies, Fiona; Armstrong, Ian R; White, Tim O; Cunningham, Colm; de Rooij, Sophia E; MacLullich, Alasdair MJ

    2014-01-01

    Objective Exaggerated central nervous system (CNS) inflammatory responses to peripheral stressors may be implicated in delirium. This study hypothesised that the IL-1β family is involved in delirium, predicting increased levels of interleukin-1β (IL-1β) and decreased IL-1 receptor antagonist (IL-1ra) in the cerebrospinal fluid (CSF) of elderly patients with acute hip fracture. We also hypothesised that Glial Fibrillary Acidic Protein (GFAP) and interferon-γ (IFN-γ) would be increased, and insulin-like growth factor 1 (IGF-1) would be decreased. Methods Participants with acute hip fracture aged > 60 (N = 43) were assessed for delirium before and 3–4 days after surgery. CSF samples were taken at induction of spinal anaesthesia. Enzyme-linked immunosorbent assays (ELISA) were used for protein concentrations. Results Prevalent delirium was diagnosed in eight patients and incident delirium in 17 patients. CSF IL-1β was higher in patients with incident delirium compared to never delirium (incident delirium 1.74 pg/ml (1.02–1.74) vs. prevalent 0.84 pg/ml (0.49–1.57) vs. never 0.66 pg/ml (0–1.02), Kruskal–Wallis p = 0.03). CSF:serum IL-1β ratios were higher in delirious than non-delirious patients. CSF IL-1ra was higher in prevalent delirium compared to incident delirium (prevalent delirium 70.75 pg/ml (65.63–73.01) vs. incident 31.06 pg/ml (28.12–35.15) vs. never 33.98 pg/ml (28.71–43.28), Kruskal–Wallis p = 0.04). GFAP was not increased in delirium. IFN-γ and IGF-1 were below the detection limit in CSF. Conclusion This study provides novel evidence of CNS inflammation involving the IL-1β family in delirium and suggests a rise in CSF IL-1β early in delirium pathogenesis. Future larger CSF studies should examine the role of CNS inflammation in delirium and its sequelae. PMID:25124807

  7. Switchable bio-inspired adhesives

    Science.gov (United States)

    Kroner, Elmar

    2015-03-01

    Geckos have astonishing climbing abilities. They can adhere to almost any surface and can run on walls and even stick to ceilings. The extraordinary adhesion performance is caused by a combination of a complex surface pattern on their toes and the biomechanics of its movement. These biological dry adhesives have been intensely investigated during recent years because of the unique combination of adhesive properties. They provide high adhesion, allow for easy detachment, can be removed residue-free, and have self-cleaning properties. Many aspects have been successfully mimicked, leading to artificial, bio-inspired, patterned dry adhesives, and were addressed and in some aspects they even outperform the adhesion capabilities of geckos. However, designing artificial patterned adhesion systems with switchable adhesion remains a big challenge; the gecko's adhesion system is based on a complex hierarchical surface structure and on advanced biomechanics, which are both difficult to mimic. In this paper, two approaches are presented to achieve switchable adhesion. The first approach is based on a patterned polydimethylsiloxane (PDMS) polymer, where adhesion can be switched on and off by applying a low and a high compressive preload. The switch in adhesion is caused by a reversible mechanical instability of the adhesive silicone structures. The second approach is based on a composite material consisting of a Nickel- Titanium (NiTi) shape memory alloy and a patterned adhesive PDMS layer. The NiTi alloy is trained to change its surface topography as a function of temperature, which results in a change of the contact area and of alignment of the adhesive pattern towards a substrate, leading to switchable adhesion. These examples show that the unique properties of bio-inspired adhesives can be greatly improved by new concepts such as mechanical instability or by the use of active materials which react to external stimuli.

  8. Switchable Adhesion in Vacuum Using Bio-Inspired Dry Adhesives.

    Science.gov (United States)

    Purtov, Julia; Frensemeier, Mareike; Kroner, Elmar

    2015-11-04

    Suction based attachment systems for pick and place handling of fragile objects like glass plates or optical lenses are energy-consuming and noisy and fail at reduced air pressure, which is essential, e.g., in chemical and physical vapor deposition processes. Recently, an alternative approach toward reversible adhesion of sensitive objects based on bioinspired dry adhesive structures has emerged. There, the switching in adhesion is achieved by a reversible buckling of adhesive pillar structures. In this study, we demonstrate that these adhesives are capable of switching adhesion not only in ambient air conditions but also in vacuum. Our bioinspired patterned adhesive with an area of 1 cm(2) provided an adhesion force of 2.6 N ± 0.2 N in air, which was reduced to 1.9 N ± 0.2 N if measured in vacuum. Detachment was induced by buckling of the structures due to a high compressive preload and occurred, independent of air pressure, at approximately 0.9 N ± 0.1 N. The switch in adhesion was observed at a compressive preload between 5.6 and 6.0 N and was independent of air pressure. The difference between maximum adhesion force and adhesion force after buckling gives a reasonable window of operation for pick and place processes. High reversibility of the switching behavior is shown over 50 cycles in air and in vacuum, making the bioinspired switchable adhesive applicable for handling operations of fragile objects.

  9. The effects of N-acetyl-cysteine and acetyl-L-carnitine on neural survival, neuroinflammation and regeneration following spinal cord injury.

    Science.gov (United States)

    Karalija, A; Novikova, L N; Kingham, P J; Wiberg, M; Novikov, L N

    2014-06-06

    Traumatic spinal cord injury induces a long-standing inflammatory response in the spinal cord tissue, leading to a progressive apoptotic death of spinal cord neurons and glial cells. We have recently demonstrated that immediate treatment with the antioxidants N-acetyl-cysteine (NAC) and acetyl-l-carnitine (ALC) attenuates neuroinflammation, induces axonal sprouting, and reduces the death of motoneurons in the vicinity of the trauma zone 4weeks after initial trauma. The objective of the current study was to investigate the effects of long-term antioxidant treatment on the survival of descending rubrospinal neurons after spinal cord injury in rats. It also examines the short- and long-term effects of treatment on apoptosis, inflammation, and regeneration in the spinal cord trauma zone. Spinal cord hemisection performed at the level C3 induced a significant loss of rubrospinal neurons 8 weeks after injury. At 2 weeks, an increase in the expression of the apoptosis-associated markers BCL-2-associated X protein (BAX) and caspase 3, as well as the microglial cell markers OX42 and ectodermal dysplasia 1 (ED1), was seen in the trauma zone. After 8 weeks, an increase in immunostaining for OX42 and the serotonin marker 5HT was detected in the same area. Antioxidant therapy reduced the loss of rubrospinal neurons by approximately 50%. Treatment also decreased the expression of BAX, caspase 3, OX42 and ED1 after 2 weeks. After 8 weeks, treatment decreased immunoreactivity for OX42, whereas it was increased for 5HT. In conclusion, this study provides further insight in the effects of treatment with NAC and ALC on descending pathways, as well as short- and long-term effects on the spinal cord trauma zone. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Directory of Open Access Journals (Sweden)

    Kelsey Roe

    Full Text Available Characterizing the mechanisms by which West Nile virus (WNV causes blood-brain barrier (BBB disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE. Infection with WNV (NY99 strain significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1 did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101 strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  11. West Nile virus-induced cell adhesion molecules on human brain microvascular endothelial cells regulate leukocyte adhesion and modulate permeability of the in vitro blood-brain barrier model.

    Science.gov (United States)

    Roe, Kelsey; Orillo, Beverly; Verma, Saguna

    2014-01-01

    Characterizing the mechanisms by which West Nile virus (WNV) causes blood-brain barrier (BBB) disruption, leukocyte infiltration into the brain and neuroinflammation is important to understand the pathogenesis of WNV encephalitis. Here, we examined the role of endothelial cell adhesion molecules (CAMs) in mediating the adhesion and transendothelial migration of leukocytes across human brain microvascular endothelial cells (HBMVE). Infection with WNV (NY99 strain) significantly induced ICAM-1, VCAM-1, and E-selectin in human endothelial cells and infected mice brain, although the levels of their ligands on leukocytes (VLA-4, LFA-1and MAC-1) did not alter. The permeability of the in vitro BBB model increased dramatically following the transmigration of monocytes and lymphocytes across the models infected with WNV, which was reversed in the presence of a cocktail of blocking antibodies against ICAM-1, VCAM-1, and E-selectin. Further, WNV infection of HBMVE significantly increased leukocyte adhesion to the HBMVE monolayer and transmigration across the infected BBB model. The blockade of these CAMs reduced the adhesion and transmigration of leukocytes across the infected BBB model. Further, comparison of infection with highly neuroinvasive NY99 and non-lethal (Eg101) strain of WNV demonstrated similar level of virus replication and fold-increase of CAMs in HBMVE cells suggesting that the non-neuropathogenic response of Eg101 is not because of its inability to infect HBMVE cells. Collectively, these results suggest that increased expression of specific CAMs is a pathological event associated with WNV infection and may contribute to leukocyte infiltration and BBB disruption in vivo. Our data further implicate that strategies to block CAMs to reduce BBB disruption may limit neuroinflammation and virus-CNS entry via 'Trojan horse' route, and improve WNV disease outcome.

  12. Wood Composite Adhesives

    Science.gov (United States)

    Gomez-Bueso, Jose; Haupt, Robert

    The global environment, in which phenolic resins are being used for wood composite manufacture, has changed significantly during the last decade. This chapter reviews trends that are driving the use and consumption of phenolic resins around the world. The review begins with recent data on volume usage and regional trends, followed by an analysis of factors affecting global markets. In a section on environmental factors, the impact of recent formaldehyde emission regulations is discussed. The section on economics introduces wood composite production as it relates to the available adhesive systems, with special emphasis on the technical requirement to improve phenolic reactivity. Advances in composite process technology are introduced, especially in regard to the increased demands the improvements place upon adhesive system performance. The specific requirements for the various wood composite families are considered in the context of adhesive performance needs. The results of research into current chemistries are discussed, with a review of recent findings regarding the mechanisms of phenolic condensation and acceleration. Also, the work regarding alternate natural materials, such as carbohydrates, lignins, tannins, and proteinaceous materials, is presented. Finally, new developments in alternative adhesive technologies are reported.

  13. Adhesive tape exfoliation

    DEFF Research Database (Denmark)

    Bohr, Jakob

    2015-01-01

    Single-crystal graphite can be cleaved by the use of an adhesive tape. This was also the initial route for obtaining graphene, a one-layer thick graphite slab. In this letter a few simple and fun considerations are presented in an attempt to shed some light on why this procedure is successful...

  14. Inflammation markers in essential hypertension.

    Science.gov (United States)

    Tsounis, Dimitrios; Bouras, Georgios; Giannopoulos, Georgios; Papadimitriou, Charalampos; Alexopoulos, Dimitrios; Deftereos, Spyridon

    2014-01-01

    Essential hypertension is a common health disorder with uncertain etiology and unclear pathophysiology. There is evidence that various systems interact in uncertain ways and mechanisms to cause hypertension. It is also well known that inflammation is a key feature in the initiation, progression and clinical implication of several cardiovascular diseases. Recently, it has become evident that the immune system and inflammatory response are also essential in the pathogenesis of hypertension. Many inflammation markers such as CRP, cytokines, and adhesion molecules have been found elevated in hypertensive patients supporting the role of inflammation in the pathogenesis of hypertension. Also, in normotensive individuals, these markers have been associated with the risk of developing hypertension, whereas in hypertensive patients they have been associated with target organ damage as well as with the risk for future cardiovascular events. Thus, understanding the role of inflammation in hypertension provides new insights for novel therapeutic approaches, targeting inflammation for the treatment of hypertension and its complications.

  15. Pathogenesis of postoperative adhesion formation

    NARCIS (Netherlands)

    Hellebrekers, B.W.J.; Kooistra, T.

    2011-01-01

    Background: Current views on the pathogenesis of adhesion formation are based on the "classical concept of adhesion formation", namely that a reduction in peritoneal fibrinolytic activity following peritoneal trauma is of key importance in adhesion development. Methods: A non-systematic literature

  16. Adhesive bonding of wood materials

    Science.gov (United States)

    Charles B. Vick

    1999-01-01

    Adhesive bonding of wood components has played an essential role in the development and growth of the forest products industry and has been a key factor in the efficient utilization of our timber resource. The largest use of adhesives is in the construction industry. By far, the largest amounts of adhesives are used to manufacture building materials, such as plywood,...

  17. Adhesion Casting In Low Gravity

    Science.gov (United States)

    Noever, David A.; Cronise, Raymond J.

    1996-01-01

    Adhesion casting in low gravity proposed as technique for making new and improved materials. Advantages of low-gravity adhesion casting, in comparison with adhesion casting in normal Earth gravity, comes from better control over, and greater uniformity of, thicknesses of liquid films that form on and adhere to solid surfaces during casting.

  18. Neuroinflammation and Oxidative Stress in Diabetic Neuropathy: Futuristic Strategies Based on These Targets

    Science.gov (United States)

    Sandireddy, Reddemma; Yerra, Veera Ganesh; Areti, Aparna; Komirishetty, Prashanth

    2014-01-01

    In Diabetes, the chronic hyperglycemia and associated complications affecting peripheral nerves are one of the most commonly occurring microvascular complications with an overall prevalence of 50–60%. Among the vascular complications of diabetes, diabetic neuropathy is the most painful and disabling, fatal complication affecting the quality of life in patients. Several theories of etiologies surfaced down the lane, amongst which the oxidative stress mediated damage in neurons and surrounding glial cell has gained attention as one of the vital mechanisms in the pathogenesis of neuropathy. Mitochondria induced ROS and other oxidants are responsible for altering the balance between oxidants and innate antioxidant defence of the body. Oxidative-nitrosative stress not only activates the major pathways namely, polyol pathway flux, advanced glycation end products formation, activation of protein kinase C, and overactivity of the hexosamine pathway, but also initiates and amplifies neuroinflammation. The cross talk between oxidative stress and inflammation is due to the activation of NF-κB and AP-1 and inhibition of Nrf2, peroxynitrite mediate endothelial dysfunction, altered NO levels, and macrophage migration. These all culminate in the production of proinflammatory cytokines which are responsible for nerve tissue damage and debilitating neuropathies. This review focuses on the relationship between oxidative stress and neuroinflammation in the development and progression of diabetic neuropathy. PMID:24883061

  19. MSCs-Derived Exosomes and Neuroinflammation, Neurogenesis and Therapy of Traumatic Brain Injury

    Science.gov (United States)

    Yang, Yongxiang; Ye, Yuqin; Su, Xinhong; He, Jun; Bai, Wei; He, Xiaosheng

    2017-01-01

    Exosomes are endosomal origin membrane-enclosed small vesicles (30–100 nm) that contain various molecular constituents including proteins, lipids, mRNAs and microRNAs. Accumulating studies demonstrated that exosomes initiated and regulated neuroinflammation, modified neurogenic niches and neurogenesis, and were even of potential significance in treating some neurological diseases. These tiny extracellular vesicles (EVs) can derive from some kinds of multipotent cells such as mesenchymal stem cells (MSCs) that have been confirmed to be a potentially promising therapy for traumatic brain injury (TBI) in experimental models and in preclinical studies. Nevertheless, subsequent studies demonstrated that the predominant mechanisms of MSCs’s contributions to brain tissue repairment and functional recovery after TBI were not the cell replacement effects but likely the secretion-based paracrine effects produced by EVs such as MSCs-derived exosomes. These nanosized exosomes derived from MSCs cannot proliferate, are easier to preserve and transfer and have lower immunogenicity, compared with transplanted exogenous MSCs. These reports revealed that MSCs-derived exosomes might promise to be a new and valuable therapeutic strategy for TBI than MSCs themselves. However, the concrete mechanisms involved in the positive effects induced by MSCs-derived exosomes in TBI are still ambiguous. In this review, we intend to explore the potential effects of MSCs-derived exosomes on neuroinflammation and neurogenesis in TBI and, especially, on therapy. PMID:28293177

  20. Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?

    Science.gov (United States)

    Faden, Alan I; Loane, David J

    2015-01-01

    It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).

  1. TGF-β1 Protection against Aβ1–42-Induced Neuroinflammation and Neurodegeneration in Rats

    Directory of Open Access Journals (Sweden)

    Wei-Xing Shen

    2014-12-01

    Full Text Available Transforming growth factor (TGF-β1, a cytokine that can be expressed in the brain, is a key regulator of the brain’s responses to injury and inflammation. Alzheimer’s disease (AD, the most common neurodegenerative disorder, involves inflammatory processes in the brain in addition to the hallmarks, amyloid-β (Aβ plaques and neurofibrillary tangles. Recently, we have shown that T-helper (Th 17 cells, a subpopulation of CD4+ T-cells with high proinflammation, also participate in the brain inflammatory process of AD. However, it is poorly known whether TGF-β1 ameliorates the lymphocyte-mediated neuroinflammation and, thereby, alleviates neurodegeneration in AD. Herein, we administered TGF-β1 via the intracerebroventricle (ICV in AD model rats, by Aβ1–42 injection in both sides of the hippocampus, to show the neuroprotection of TGF-β1. The TGF-β1 administration after the Aβ1–42 injection ameliorated cognitive deficit and neuronal loss and apoptosis, reduced amyloid precursor protein (APP expression, elevated protein phosphatase (PP2A expression, attenuated glial activation and alleviated the imbalance of the pro-inflammatory/anti-inflammatory responses of T-lymphocytes, compared to the Aβ1–42 injection alone. These findings demonstrate that TGF-β1 provides protection against AD neurodegeneration and suggest that the TGF-β1 neuroprotection is implemented by the alleviation of glial and T-cell-mediated neuroinflammation.

  2. Hippocampal FGF-2 and BDNF overexpression attenuates epileptogenesis-associated neuroinflammation and reduces spontaneous recurrent seizures

    Directory of Open Access Journals (Sweden)

    Osculati Francesco

    2010-11-01

    Full Text Available Abstract Under certain experimental conditions, neurotrophic factors may reduce epileptogenesis. We have previously reported that local, intrahippocampal supplementation of fibroblast growth factor-2 (FGF-2 and brain-derived neurotrophic factor (BDNF increases neurogenesis, reduces neuronal loss, and reduces the occurrence of spontaneous seizures in a model of damage-associated epilepsy. Here, we asked if these possibly anti-epileptogenic effects might involve anti-inflammatory mechanisms. Thus, we used a Herpes-based vector to supplement FGF-2 and BDNF in rat hippocampus after pilocarpine-induced status epilepticus that established an epileptogenic lesion. This model causes intense neuroinflammation, especially in the phase that precedes the occurrence of spontaneous seizures. The supplementation of FGF-2 and BDNF attenuated various parameters of inflammation, including astrocytosis, microcytosis and IL-1β expression. The effect appeared to be most prominent on IL-1β, whose expression was almost completely prevented. Further studies will be needed to elucidate the molecular mechanism(s for these effects, and for that on IL-1β in particular. Nonetheless, the concept that neurotrophic factors affect neuroinflammation in vivo may be highly relevant for the understanding of the epileptogenic process.

  3. Neuroinflammation in traumatic brain injury: A chronic response to an acute injury

    Directory of Open Access Journals (Sweden)

    Samantha J Schimmel

    2017-01-01

    Full Text Available Every year, approximately 1.4 million US citizens visit emergency rooms for traumatic brain injuries. Formerly known as an acute injury, chronic neurodegenerative symptoms such as compromised motor skills, decreased cognitive abilities, and emotional and behavioral changes have caused the scientific community to consider chronic aspects of the disorder. The injury causing impact prompts multiple cell death processes, starting with neuronal necrosis, and progressing to various secondary cell death mechanisms. Secondary cell death mechanisms, including excitotoxicity, oxidative stress, mitochondrial dysfunction, blood–brain barrier disruption, and inflammation accompany chronic traumatic brain injury (TBI and often contribute to long-term disabilities. One hallmark of both acute and chronic TBI is neuroinflammation. In acute stages, neuroinflammation is beneficial and stimulates an anti-inflammatory response to the damage. Conversely, in chronic TBI, excessive inflammation stimulates the aforementioned secondary cell death. Converting inflammatory cells from pro-inflammatory to anti-inflammatory may expand the therapeutic window for treating TBI, as inflammation plays a role in all stages of the injury. By expanding current research on the role of inflammation in TBI, treatment options and clinical outcomes for afflicted individuals may improve. This paper is a review article. Referred literature in this paper has been listed in the references section. The data sets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  4. Cytokines and Chemokines at the Crossroads of Neuroinflammation, Neurodegeneration, and Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    Geeta Ramesh

    2013-01-01

    Full Text Available Cytokines and chemokines are proteins that coordinate the immune response throughout the body. The dysregulation of cytokines and chemokines is a central feature in the development of neuroinflammation, neurodegeneration, and demyelination both in the central and peripheral nervous systems and in conditions of neuropathic pain. Pathological states within the nervous system can lead to activation of microglia. The latter may mediate neuronal and glial cell injury and death through production of proinflammatory factors such as cytokines and chemokines. These then help to mobilize the adaptive immune response. Although inflammation may induce beneficial effects such as pathogen clearance and phagocytosis of apoptotic cells, uncontrolled inflammation can result in detrimental outcomes via the production of neurotoxic factors that exacerbate neurodegenerative pathology. In states of prolonged inflammation, continual activation and recruitment of effector cells can establish a feedback loop that perpetuates inflammation and ultimately results in neuronal injury. A critical balance between repair and proinflammatory factors determines the outcome of a neurodegenerative process. This review will focus on how cytokines and chemokines affect neuroinflammation and disease pathogenesis in bacterial meningitis and brain abscesses, Lyme neuroborreliosis, human immunodeficiency virus encephalitis, and neuropathic pain.

  5. Molecular imaging of neuroinflammation in Alzheimer's disease and mild cognitive impairment.

    Science.gov (United States)

    Knezevic, Dunja; Mizrahi, Romina

    2018-01-03

    Neuroinflammatory changes have been demonstrated to be an important feature of Alzheimer's disease (AD); however, the exact role of neuroinflammation and its progression during disease is still not well understood. One of the main drivers of the neuroinflammatory process are microglial cells. Positron Emission Tomography allows for the quantification of microglial activation by labelling the Translocator Protein 18kDa (TSPO), which becomes overexpressed upon activation of microglial cells. Several radioligands have been designed to target TSPO and have been studied in-vivo in AD populations. While most studies have shown important increases in TSPO binding in AD populations compared to healthy volunteers, whether the neuroinflammatory progress occurs early on or later during disease is still unclear. In order to investigate the early changes in neuroinflammation, studies have sought to investigate microglial activation in patients with mild cognitive impairment (MCI), which is defined as a transitional stage between normal aging and dementia. In this prodromal population, conflicting results have been reported with some studies reporting increased binding in MCI, while others demonstrate no differences from controls. Here we review the TSPO PET studies in AD and MCI populations and discuss the important methodological considerations of imaging microglial activation. Copyright © 2017. Published by Elsevier Inc.

  6. Methylene Blue Mitigates Acute Neuroinflammation after Spinal Cord Injury through Inhibiting NLRP3 Inflammasome Activation in Microglia.

    Science.gov (United States)

    Lin, Zhi-Hang; Wang, Si-Yuan; Chen, Li-Li; Zhuang, Jia-Yuan; Ke, Qing-Feng; Xiao, Dan-Rui; Lin, Wen-Ping

    2017-01-01

    The spinal cord injury (SCI) is a detrimental neurological disease involving the primary mechanical injury and secondary inflammatory damage. Curtailing the detrimental neuroinflammation would be beneficial for spinal cord function recovery. Microglia reside in the spinal cord and actively participate in the onset, progression and perhaps resolution of post-SCI neuroinflammation. In the current study, we tested the effects of methylene blue on microglia both in vitro and in a rat SCI model. We found that methylene blue inhibited the protein levels of IL-1β and IL-18 rather than their mRNA levels in activated microglia. Further investigation indicated that methylene blue deceased the activation of NLRP3 inflammasome and NLRC4 inflammasome in microglia in vitro . Moreover, in the rat SCI model, the similar effect of methylene blue on post-SCI microglia was also observed, except that the activation of NLRC4 inflammasome was not seen. The inhibition of microglia NLRP3 inflammasome was associated with down-regulation of intracellular reactive oxygen species (ROS). The administration of methylene blue mitigated the overall post-SCI neuroinflammation, demonstrated by decreased pro-inflammatory cytokine production and leukocyte infiltrates. Consequently, the neuronal apoptosis was partially inhibited and the hind limb locomotor function was ameliorated by methylene blue treatment. Our research highlights the role of methylene blue in inhibiting post-SCI neuroinflammation, and suggests that methylene blue might be used for SCI therapy.

  7. Time-Dependent Compensatory Responses to Chronic Neuroinflammation in Hippocampus and Brainstem: The Potential Role of Glutamate Neurotransmission.

    Science.gov (United States)

    Brothers, Holly M; Bardou, Isabelle; Hopp, Sarah C; Marchalant, Yannick; Kaercher, Roxanne M; Turner, Sarah M; Mitchem, Mollie R; Kigerl, Kristina; Wenk, Gary L

    2013-03-28

    Chronic neuroinflammation is characteristic of neurodegenerative diseases and is present during very early stages, yet significant pathology and behavioral deficits do not manifest until advanced age. We investigated the consequences of experimentally-induced chronic neuroinflammation within the hippocampus and brainstem of young (4 mo) F-344 rats. Lipopolysaccharide (LPS) was infused continuously into the IV th ventricle for 2, 4 or 8 weeks. The number of MHC II immunoreactive microglia in the brain continued to increase throughout the infusion period. In contrast, performance in the Morris water maze was impaired after 4 weeks but recovered by 8 weeks. Likewise, a transient loss of tyrosine hydroxylase immunoreactivity in the substantia nigra and locus coeruleus was observed after 2 weeks, but returned to control levels by 4 weeks of continuous LPS infusion. These data suggest that direct activation of microglia is sufficient to drive, but not sustain, spatial memory impairment and a decrease in tyrosine hydroxylase production in young rats. Our previous studies suggest that chronic neuroinflammation elevates extracellular glutamate and that this elevation underlies the spatial memory impairment. In the current study, increased levels of GLT1 and SNAP25 in the hippocampus corresponded with the resolution of performance deficit. Increased expression of SNAP25 is consistent with reduced glutamate release from axonal terminals while increased GLT1 is consistent with enhanced clearance of extracellular glutamate. These data demonstrate the capacity of the brain to compensate for the presence of chronic neuroinflammation, despite continued activation of microglia, through changes in the regulation of the glutamatergic system.

  8. trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation

    Directory of Open Access Journals (Sweden)

    Yan Fu

    2017-01-01

    Full Text Available Background. Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled. trans-cinnamaldehyde (TCA isolated from the stem bark of Cinnamomum cassia possesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells. Results. To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS- induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1β and recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects. Conclusions. Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

  9. mTOR pathway inhibition prevents neuroinflammation and neuronal death in a mouse model of cerebral palsy.

    Science.gov (United States)

    Srivastava, Isha N; Shperdheja, Jona; Baybis, Marianna; Ferguson, Tanya; Crino, Peter B

    2016-01-01

    Mammalian target of rapamycin (mTOR) pathway signaling governs cellular responses to hypoxia and inflammation including induction of autophagy and cell survival. Cerebral palsy (CP) is a neurodevelopmental disorder linked to hypoxic and inflammatory brain injury however, a role for mTOR modulation in CP has not been investigated. We hypothesized that mTOR pathway inhibition would diminish inflammation and prevent neuronal death in a mouse model of CP. Mouse pups (P6) were subjected to hypoxia-ischemia and lipopolysaccharide-induced inflammation (HIL), a model of CP causing neuronal injury within the hippocampus, periventricular white matter, and neocortex. mTOR pathway inhibition was achieved with rapamycin (an mTOR inhibitor; 5mg/kg) or PF-4708671 (an inhibitor of the downstream p70S6kinase, S6K, 75 mg/kg) immediately following HIL, and then for 3 subsequent days. Phospho-activation of the mTOR effectors p70S6kinase and ribosomal S6 protein and expression of hypoxia inducible factor 1 (HIF-1α) were assayed. Neuronal cell death was defined with Fluoro-Jade C (FJC) and autophagy was measured using Beclin-1 and LC3II expression. Iba-1 labeled, activated microglia were quantified. Neuronal death, enhanced HIF-1α expression, and numerous Iba-1 labeled, activated microglia were evident at 24 and 48 h following HIL. Basal mTOR signaling, as evidenced by phosphorylated-S6 and -S6K levels, was unchanged by HIL. Rapamycin or PF-4,708,671 treatment significantly reduced mTOR signaling, neuronal death, HIF-1α expression, and microglial activation, coincident with enhanced expression of Beclin-1 and LC3II, markers of autophagy induction. mTOR pathway inhibition prevented neuronal death and diminished neuroinflammation in this model of CP. Persistent mTOR signaling following HIL suggests a failure of autophagy induction, which may contribute to neuronal death in CP. These results suggest that mTOR signaling may be a novel therapeutic target to reduce neuronal cell death in

  10. Management of adhesive capsulitis

    Directory of Open Access Journals (Sweden)

    Stupay KL

    2015-08-01

    Full Text Available Kristen L Stupay,1 Andrew S Neviaser2 1Tulane University School of Medicine, New Orleans, LA, USA; 2George Washington University Medical Faculty Associates, Washington, DC, USA Abstract: Adhesive capsulitis of the shoulder is a condition of capsular contracture that reduces both active and passive glenohumeral motion. The cause of adhesive capsulitis is not known but it is strongly associated with endocrine abnormalities such as diabetes. Diverse terminology and the absence of definitive criteria for diagnosis make evaluating treatment modalities difficult. Many treatment methods have been reported, most with some success, but few have been proved to alter the natural course of this disease. Most afflicted patients will achieve acceptable shoulder function without surgery. Those who remain debilitated after 8–12 months are reasonable candidates for invasive treatments. Here, the various treatment methods and the data to support their use are reviewed. Keywords: frozen shoulder, stiff shoulder, periarthritis, painful shoulder 

  11. Adhesion between cerebroside bilayers.

    Science.gov (United States)

    Kulkarni, K; Snyder, D S; McIntosh, T J

    1999-11-16

    The structure, hydration properties, and adhesion energy of the membrane glycolipid galactosylceramide (GalCer) were studied by osmotic stress/X-ray diffraction analysis.(1) Fully hydrated GalCer gave a repeat period of 67 A, which decreased less than 2 A with application of applied osmotic pressures as large as 1.6 x 10(9) dyn/cm(2). These results, along with the invariance of GalCer structure obtained by a Fourier analysis of the X-ray data, indicated that there was an extremely narrow fluid space (less than the diameter of a single water molecule) between fully hydrated cerebroside bilayers. Electron density profiles showed that the hydrocarbon chains from apposing GalCer monolayers partially interdigitated in the center of the bilayer. To obtain information on the adhesive properties of GalCer bilayers, we incorporated into the bilayer various mole ratios of the negatively charged lipid dipalmitoylphosphatidylglycerol (DPPG) to provide known electrostatic repulsion between the bilayers. Although 17 and 20 mol % DPPG swelled (disjoined) the GalCer bilayers by an amount predictable from electrostatic double-layer theory, 5, 10, 13, and 15 mol % DPPG did not disjoin the bilayers. By calculating the magnitude of the electrostatic pressure necessary to disjoin the bilayers, we estimated the adhesion energy for GalCer bilayers to be about -1.5 erg/cm(2), a much larger value than that previously measured for phosphatidylcholine bilayers. The observed discontinuous disjoining with increased electrostatic pressure and this relatively large value for adhesion energy indicated the presence of an attractive interaction, in addition to van der Waals attraction, between cerebroside bilayers. Possible attractive interactions are hydrogen bond formation and hydrophobic interactions between the galactose headgroups of apposing GalCer bilayers.

  12. Syndecans and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Chen, L; Woods, A

    2001-01-01

    Now that transmembrane signaling through primary cell-matrix receptors, integrins, is being elucidated, attention is turning to how integrin-ligand interactions can be modulated. Syndecans are transmembrane proteoglycans implicated as coreceptors in a variety of physiological processes, including...... cell adhesion, migration, response to growth factors, development, and tumorigenesis. This review will describe this family of proteoglycans in terms of their structures and functions and their signaling in conjunction with integrins, and indicate areas for future research....

  13. Cell adhesion on nanotopography

    Science.gov (United States)

    Tsai, Irene; Kimura, Masahiro; Stockton, Rebecca; Jacobson, Bruce; Russell, Thomas

    2003-03-01

    Cell adhesion, a key element in understanding the cell-biomaterial interactions, underpins proper cell growth, function and survival. Understanding the parameters influencing cell adhesion is critical for applications in biosensors, implants and bioreactors. A gradient surface is used to study the effect of the surface topography on cell adhesion. A gradient surface is generated by block copolymer and homopolymer blends. The two homopolymers will phase separate on the micron scale and gradually decrease to nano-scale by the microphase separation of the diblock. Gradient surfaces offer a unique opportunity to probe lateral variations in the topography and interactions. Using thin films of mixtures of diblock copolymers of PS-b-MMA with PS and PMMA homopolymers, where the concentration of the PS-b-MMA varies across the surface, a gradient in the size scale of the morphology, from the nanoscopic to microscopic, was produced. By UV exposure, the variation in morphology translated into a variation in topography. The extent of cell spreading and cytoskeleton formation was investigated and marked dependence on the length scale of the surface topography was found.

  14. [Fulminant adhesive arachnoiditis].

    Science.gov (United States)

    Tomczykiewicz, Kazimierz; Stępień, Adam; Staszewski, Jacek; Sadowska, Marta; Bogusławska-Walecka, Romana

    2012-01-01

    Adhesive arachnoiditis is a rare disease with insidious course. It causes damage of the spinal cord and nerve roots. The causes of adhesive arachnoiditis include earlier traumatic injury of the spinal cord, surgery, intrathecal administration of therapeutic substances (e.g. anaesthetics, chemotherapy) or contrast media, bleeding, and inflammation. It can also be idiopathic or iatrogenic. We present the case of a 42-year-old patient with fulminant adhesive arachnoiditis which was provoked by spinal surgery and caused severe neurological disability with profound, progressive, flaccid paraparesis and bladder dysfunction. The electromyography (EMG) showed serious damage of nerves of both lower limbs at the level of motor roots L2-S2 and damage of the motor neuron at the level of Th11-Th12 on the right side. Magnetic resonance imaging of the lumbosacral and thoracic part of the spinal cord demonstrated cystic liquid spaces in the lumen of the dural sac in the bottom part of the cervical spine and at the Th2-Th10 level, modelling the lateral and anterior surface of the cord. Because of the vast lesions, surgery could not be performed. Conservative treatment and rehabilitation brought only a small clinical improvement.

  15. Development of phosphorylated adhesives

    Science.gov (United States)

    Bilow, N.; Giants, T. W.; Jenkins, R. K.; Campbell, P. L.

    1983-01-01

    The synthesis of epoxy prepolymers containing phosphorus was carried out in such a manner as to provide adhesives containing at least 5 percent of this element. The purpose of this was to impart fire retardant properties to the adhesive. The two epoxy derivatives, bis(4-glycidyl-oxyphenyl)phenylphosphine oxide and bis(4-glycidyl-2-methoxyphenyl)phenylphosphonate, and a curing agent, bis(3-aminophenyl)methylphosphine oxide, were used in conjunction with one another and along with conventional epoxy resins and curing agents to bond Tedlar and Polyphenylethersulfone films to Kerimid-glass syntactic foam-filled honeycomb structures. Elevated temperatures are required to cure the epoxy resins with the phosphorus-contaning diamine; however, when Tedlar is being bonded, lower curing temperatures must be used to avoid shrinkage and the concomitant formation of surface defects. Thus, the phosphorus-containing aromatic amine curing agent cannot be used alone, although it is possible to use it in conjunction with an aliphatic amine which would allow lower cure temperatures to be used. The experimental epoxy resins have not provided adhesive bonds quite as strong as those provided by Epon 828 when compared in peel tests, but the differences are not very significant. It should be noted, if optimum properties are to be realized. In any case the fire retardant characteristics of the neat resin systems obtained are quite pronounced, since in most cases the self-extinguishing properties are evident almost instantly when specimens are removed from a flame.

  16. Imaging neuroinflammation in gray and white matter in schizophrenia: an in-vivo PET study with [18F]-FEPPA.

    Science.gov (United States)

    Kenk, Miran; Selvanathan, Thiviya; Rao, Naren; Suridjan, Ivonne; Rusjan, Pablo; Remington, Gary; Meyer, Jeffrey H; Wilson, Alan A; Houle, Sylvain; Mizrahi, Romina

    2015-01-01

    Neuroinflammation and abnormal immune responses have been implicated in schizophrenia (SCZ). Past studies using positron emission tomography (PET) that examined neuroinflammation in patients with SCZ in vivo using the translocator protein 18kDa (TSPO) target were limited by the insensitivity of the first-generation imaging agent [(11)C]-PK11195, scanners used, and the small sample sizes studied. Present study uses a novel second-generation TSPO PET radioligand N-acetyl-N-(2-[(18)F]fluoroethoxybenzyl)-2-phenoxy-5-pyridinamine ([(18)F]-FEPPA) to evaluate whether there is increased neuroinflammation in patients with SCZ. A cross-sectional study was performed using [(18)F]-FEPPA and a high-resolution research tomograph (HRRT). Eighteen patients with SCZ with ongoing psychotic symptoms and 27 healthy volunteers (HV) were recruited from a tertiary psychiatric clinical setting and the community, respectively. All participants underwent [(18)F]-FEPPA PET and magnetic resonance imaging, and PET data were analyzed to obtain [(18)F]-FEPPA total volume of distribution (VT) using a 2-tissue compartment model with an arterial plasma input function, as previously validated. All subjects were classified as high-, medium- or low-affinity [(18)F]-FEPPA binders on the basis of rs6971 polymorphism, and genotype information was incorporated into the analyses of imaging outcomes. No significant differences in neuroinflammation indexed as [(18)F]-FEPPA VT were observed between groups in either gray (F(1,39) = 0.179, P = .674) or white matter regions (F(1,38) = 0.597, P = .445). The lack of significant difference in neuroinflammation in treated patients with SCZ in the midst of a psychotic episode and HV suggests that neuroinflammatory processes may take place early in disease progression or are affected by antipsychotic treatment. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please

  17. Leukotriene-mediated neuroinflammation, toxic brain damage, and neurodegeneration in acute methanol poisoning.

    Science.gov (United States)

    Zakharov, Sergey; Kotikova, Katerina; Nurieva, Olga; Hlusicka, Jiri; Kacer, Petr; Urban, Pavel; Vaneckova, Manuela; Seidl, Zdenek; Diblik, Pavel; Kuthan, Pavel; Navratil, Tomas; Pelclova, Daniela

    2017-04-01

    The role of neuroinflammation in methanol-induced toxic brain damage has not been studied. We studied acute concentrations and the dynamics of leukotrienes (LT) in serum in hospitalized patients with acute methanol poisoning and in survivors. Series of acute cysteinyl-LT and LTB4 concentration measurements were performed in 28/101 hospitalized patients (mean observation time: 88 ± 20 h). In 36 survivors, control LT measurements were performed 2 years after discharge. The acute maximum (Cmax) LT concentrations were higher than concentrations in survivors: Cmax for LTC4 was 80.7 ± 5.6 versus 47.9 ± 4.5 pg/mL; for LTD4, 51.0 ± 6.6 versus 23.1 ± 2.1 pg/mL; for LTE4, 64.2 ± 6.0 versus 26.2 ± 3.9 pg/mL; for LTB4, 59.8 ± 6.2 versus 27.2 ± 1.4 pg/mL (all p  0.05). The mean decrease in LT concentration was 30.9 ± 9.0 pg/mL for LTC4, 26.3 ± 8.6 pg/mL for LTD4, 37.3 ± 6.4 pg/mL for LTE4, and 32.0 ± 8.8 pg/mL for LTB4. Our findings suggest that leukotriene-mediated neuroinflammation may play an important role in the mechanisms of toxic brain damage in acute methanol poisoning in humans. Acute elevation of LT concentrations was moderate, transitory, and was not followed by chronic neuroinflammation in survivors.

  18. Dental adhesives of the future.

    Science.gov (United States)

    Tay, Franklin R; Pashley, David H

    2002-01-01

    The current trend in the development of dentin adhesives attempts to simplify bonding steps and make them more user-friendly. However, optimizing speed and efficiency should be accomplished without major tradeoffs in the quality or durability of resin bonds. Although dentin adhesives have improved tremendously over the past decade, postoperative sensitivity, incomplete marginal seal, premature bond degradation, biocompatibility, and compromised bonding to abnormal substrates are still considered potential problems associated with their use. Advances in different scientific disciplines will enrich the pool from which ideas may be drawn in designing future dentin adhesives. It is probably on the molecular level that we will see the greatest expansion of horizons. With the advances in biomimetics, future dentin adhesive monomers may contain domains derived from protein-based, underwater bioadhesives secreted by aquatic animals such as mussels and barnacles, making them less dependent on the surface energy of the bonding substrates as well as less susceptible to hydrolytic degradation. As adhesive joints produced by contemporary adhesives are brittle in nature, future adhesive design may incorporate biomimetic intermediate-strength domains that can undergo stepwise reversible unfolding in response to varying functional stress levels before ultimate catastrophic failure of the adhesive joint occurs. These domains may also re-establish folded configurations on stress relaxation, making the adhesive both strong and tough. Using the concept of controlled release, future adhesives may contain fluorescent biosensors that can detect pH changes around leaking restorations. They may even have the capacity to heal autonomously, in response to microcracks formed by functional stresses within the adhesive joint. The ability to self-diagnose and self-repair will increase the life expectancy of adhesive restorations. Future dentin adhesives may also assume a more instrumental role

  19. Adhesion prevention in gynaecological surgery.

    Science.gov (United States)

    Robertson, Deborah; Lefebvre, Guylaine

    2010-06-01

    To review the etiology and incidence of and associative factors in the formation of adhesions following gynaecological surgery. To review evidence for the use of available means of adhesion prevention following gynaecological surgery. Women undergoing pelvic surgery are at risk of developing abdominal and/or pelvic adhesive disease postoperatively. Surgical technique and commercial adhesion prevention systems may decrease the risk of postoperative adhesion formation. The outcomes measured are the incidence of postoperative adhesions, complications related to the formation of adhesions, and further intervention relative to adhesive disease. Medline, EMBASE, and The Cochrane Library were searched for articles published in English from 1990 to March 2009, using appropriate controlled vocabulary and key words. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, cohort studies, and meta-analyses specifically addressing postoperative adhesions, adhesion prevention, and adhesive barriers. Searches were updated on a regular basis and incorporated in the guideline to March 2009. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care SUMMARY STATEMENTS: 1. Meticulous surgical technique is a means of preventing adhesions. This includes minimizing tissue trauma, achieving optimal hemostasis, minimizing the risk of infection, and avoiding contaminants (e.g., fecal matter) and the use of foreign materials (e.g., talcum powder) when possible. (II-2). 2. The risk of adhesions increases with the total number of abdominal and pelvic surgeries performed on one patient; every

  20. Annual research review: The neuroinflammation hypothesis for stress and psychopathology in children--developmental psychoneuroimmunology.

    Science.gov (United States)

    O'Connor, Thomas G; Moynihan, Jan A; Caserta, Mary T

    2014-06-01

    Experimental animal and adult human data suggest that stress exposure is associated with alterations in immune system function that may underlie increased susceptibility to disease and behavioral disorders. The implications of these data for child psychology and psychiatry are not yet clear. The current review seeks to distil and translate the relevant animal and adult human work to children to advance a developmental model of psychoneuroimmunology. In addition to reviewing key specific findings, we consider biological/conceptual models and technical aspects of psychoneuroimmunology work in pediatric populations, and outline the rationales and advantages of integrating hypotheses concerning neuroinflammation in developmental studies of psychopathology. © 2013 The Authors. Journal of Child Psychology and Psychiatry. © 2013 Association for Child and Adolescent Mental Health.

  1. Neuroinflammation at the interface of depression and cardiovascular disease: Evidence from rodent models of social stress

    Directory of Open Access Journals (Sweden)

    Julie E. Finnell

    2016-10-01

    Full Text Available A large body of evidence has emerged linking stressful experiences, particularly from one's social environment, with psychiatric disorders. However, vast individual differences emerge in susceptibility to developing stress-related pathology which may be due to distinct differences in the inflammatory response to social stress. Furthermore, depression is an independent risk factor for cardiovascular disease, another inflammatory-related disease, and results in increased mortality in depressed patients. This review is focused on discussing evidence for stress exposure resulting in persistent or sensitized inflammation in one individual while this response is lacking in others. Particular focus will be directed towards reviewing the literature underlying the impact that neuroinflammation has on neurotransmitters and neuropeptides that could be involved in the pathogenesis of comorbid depression and cardiovascular disease. Finally, the theme throughout the review will be to explore the notion that stress-induced inflammation is a key player in the high rate of comorbidity between psychosocial disorders and cardiovascular disease.

  2. Gadofluorine M-enhanced MRI shows involvement of circumventricular organs in neuroinflammation

    Directory of Open Access Journals (Sweden)

    Glumm Robert

    2010-10-01

    Full Text Available Abstract Background Circumventricular organs (CVO are cerebral areas with incomplete endothelial blood-brain barrier (BBB and therefore regarded as "gates to the brain". During inflammation, they may exert an active role in determining immune cell recruitment into the brain. Methods In a longitudinal study we investigated in vivo alterations of CVO during neuroinflammation, applying Gadofluorine M- (Gf enhanced magnetic resonance imaging (MRI in experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. SJL/J mice were monitored by Gadopentate dimeglumine- (Gd-DTPA and Gf-enhanced MRI after adoptive transfer of proteolipid-protein-specific T cells. Mean Gf intensity ratios were calculated individually for different CVO and correlated to the clinical disease course. Subsequently, the tissue distribution of fluorescence-labeled Gf as well as the extent of cellular inflammation was assessed in corresponding histological slices. Results We could show that the Gf signal intensity of the choroid plexus, the subfornicular organ and the area postrema increased significantly during experimental autoimmune encephalomyelitis, correlating with (1 disease severity and (2 the delay of disease onset after immunization. For the choroid plexus, the extent of Gf enhancement served as a diagnostic criterion to distinguish between diseased and healthy control mice with a sensitivity of 89% and a specificity of 80%. Furthermore, Gf improved the detection of lesions, being particularly sensitive to optic neuritis. In correlated histological slices, Gf initially accumulated in the extracellular matrix surrounding inflammatory foci and was subsequently incorporated by macrophages/microglia. Conclusion Gf-enhanced MRI provides a novel highly sensitive technique to study cerebral BBB alterations. We demonstrate for the first time in vivo the involvement of CVO during the development of neuroinflammation.

  3. Antarctic Krill Oil Diet Protects against Lipopolysaccharide-Induced Oxidative Stress, Neuroinflammation and Cognitive Impairment

    Directory of Open Access Journals (Sweden)

    Ji Yeon Choi

    2017-11-01

    Full Text Available Oxidative stress and neuroinflammation are implicated in the development and pathogenesis of Alzheimer’s disease (AD. Here, we investigated the anti-inflammatory and antioxidative effects of krill oil. Oil from Euphausia superba (Antarctic krill, an Antarctic marine species, is rich in eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA. We examined whether krill oil diet (80 mg/kg/day for one month prevents amyloidogenesis and cognitive impairment induced by intraperitoneal lipopolysaccharide (LPS (250 µg/kg, seven times daily injections in AD mice model and found that krill oil treatment inhibited the LPS-induced memory loss. We also found that krill oil treatment inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 and decreased reactive oxygen species (ROS and malondialdehyde levels. Krill oil also suppresses IκB degradation as well as p50 and p65 translocation into the nuclei of LPS-injected mice brain cells. In association with the inhibitory effect on neuroinflammation and oxidative stress, krill oil suppressed amyloid beta (1–42 peptide generation by the down-regulating APP and BACE1 expression in vivo. We found that eicosapentaenoic acid (EPA and docosahexaenoic acid (DHA (50 and 100 µM dose-dependently decreased LPS-induced nitric oxide and ROS generation, and COX-2 and iNOS expression as well as nuclear factor-κB activity in cultured microglial BV-2 cells. These results suggest that krill oil ameliorated impairment via anti-inflammatory, antioxidative, and anti-amyloidogenic mechanisms.

  4. Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment.

    Science.gov (United States)

    Smolek, Tomas; Madari, Aladar; Farbakova, Jana; Kandrac, Ondrej; Jadhav, Santosh; Cente, Martin; Brezovakova, Veronika; Novak, Michal; Zilka, Norbert

    2016-03-01

    Canine cognitive impairment syndrome (CDS) represents a group of symptoms related to the aging of the canine brain. These changes ultimately lead to a decline of memory function and learning abilities, alteration of social interaction, impairment of normal housetraining, and changes in sleep-wake cycle and general activity. We have clinically examined 215 dogs, 28 of which underwent autopsy. With canine brains, we performed extensive analysis of pathological abnormalities characteristic of human Alzheimer's disease and frontotemporal lobar degeneration, including β-amyloid senile plaques, tau neurofibrillary tangles, and fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP43) inclusions. Most demented dogs displayed senile plaques, mainly in the frontal and temporal cortex. Tau neurofibrillary inclusions were found in only one dog. They were identified with antibodies used to detect tau neurofibrillary lesions in the human brain. The inclusions were also positive for Gallyas silver staining. As in humans, they were distributed mainly in the entorhinal cortex, hippocampus, and temporal cortex. On the other hand, FUS and TDP43 aggregates were not present in any of the examined brain samples. We also found that CDS was characterized by the presence of reactive and senescent microglial cells in the frontal cortex. Our transcriptomic study revealed a significant dysregulation of genes involved in neuroinflammation. Finally, we analyzed tau phosphoproteome in the synaptosomes. Proteomic studies revealed a significant increase of hyperphosphorylated tau in synaptosomes of demented dogs compared with nondemented dogs. This study suggests that cognitive decline in dogs is related to the tau synaptic impairment and neuroinflammation. J. Comp. Neurol. 524:874-895, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  5. Antarctic Krill Oil Diet Protects against Lipopolysaccharide-Induced Oxidative Stress, Neuroinflammation and Cognitive Impairment.

    Science.gov (United States)

    Choi, Ji Yeon; Jang, Jun Sung; Son, Dong Ju; Im, Hyung-Sik; Kim, Ji Yeong; Park, Joung Eun; Choi, Won Rak; Han, Sang-Bae; Hong, Jin Tae

    2017-11-28

    Oxidative stress and neuroinflammation are implicated in the development and pathogenesis of Alzheimer's disease (AD). Here, we investigated the anti-inflammatory and antioxidative effects of krill oil. Oil from Euphausia superba (Antarctic krill), an Antarctic marine species, is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We examined whether krill oil diet (80 mg/kg/day for one month) prevents amyloidogenesis and cognitive impairment induced by intraperitoneal lipopolysaccharide (LPS) (250 µg/kg, seven times daily) injections in AD mice model and found that krill oil treatment inhibited the LPS-induced memory loss. We also found that krill oil treatment inhibited the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and decreased reactive oxygen species (ROS) and malondialdehyde levels. Krill oil also suppresses IκB degradation as well as p50 and p65 translocation into the nuclei of LPS-injected mice brain cells. In association with the inhibitory effect on neuroinflammation and oxidative stress, krill oil suppressed amyloid beta (1-42) peptide generation by the down-regulating APP and BACE1 expression in vivo. We found that eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (50 and 100 µM) dose-dependently decreased LPS-induced nitric oxide and ROS generation, and COX-2 and iNOS expression as well as nuclear factor-κB activity in cultured microglial BV-2 cells. These results suggest that krill oil ameliorated impairment via anti-inflammatory, antioxidative, and anti-amyloidogenic mechanisms.

  6. Elucidation of Relevant Neuroinflammation Mechanisms Using Gene Expression Profiling in Patients with Amyotrophic Lateral Sclerosis.

    Directory of Open Access Journals (Sweden)

    Yu Hui Won

    Full Text Available Amyotrophic lateral sclerosis (ALS is a progressive neurodegenerative disorder characterized by damage of motor neurons. Recent reports indicate that inflammatory responses occurring within the central nervous system contribute to the pathogenesis of ALS. We aimed to investigate disease-specific gene expression associated with neuroinflammation by conducting transcriptome analysis on fibroblasts from three patients with sporadic ALS and three normal controls. Several pathways were found to be upregulated in patients with ALS, among which the toll-like receptor (TLR and NOD-like receptor (NLR signaling pathways are related to the immune response. Genes-toll-interacting protein (TOLLIP, mitogen-activated protein kinase 9 (MAPK9, interleukin-1β (IL-1β, interleukin-8 (IL-8, and chemokine (C-X-C motif ligand 1 (CXCL1-related to these two pathways were validated using western blotting. This study validated the genes that are associated with TLR and NLR signaling pathways from different types of patient-derived cells. Not only fibroblasts but also induced pluripotent stem cells (iPSCs and neural rosettes from the same origins showed similar expression patterns. Furthermore, expression of TOLLIP, a regulator of TLR signaling pathway, decreased with cellular aging as judged by changes in its expression through multiple passages. TOLLIP expression was downregulated in ALS cells under conditions of inflammation induced by lipopolysaccharide. Our data suggest that the TLR and NLR signaling pathways are involved in pathological innate immunity and neuroinflammation associated with ALS and that TOLLIP, MAPK9, IL-1β, IL-8, and CXCL1 play a role in ALS-specific immune responses. Moreover, changes of TOLLIP expression might be associated with progression of ALS.

  7. CLEC5A regulates Japanese encephalitis virus-induced neuroinflammation and lethality.

    Directory of Open Access Journals (Sweden)

    Szu-Ting Chen

    Full Text Available CLEC5A/MDL-1, a member of the myeloid C-type lectin family expressed on macrophages and neutrophils, is critical for dengue virus (DV-induced hemorrhagic fever and shock syndrome in Stat1⁻/⁻ mice and ConA-treated wild type mice. However, whether CLEC5A is involved in the pathogenesis of viral encephalitis has not yet been investigated. To investigate the role of CLEC5A to regulate JEV-induced neuroinflammation, antagonistic anti-CLEC5A mAb and CLEC5A-deficient mice were generated. We find that Japanese encephalitis virus (JEV directly interacts with CLEC5A and induces DAP12 phosphorylation in macrophages. In addition, JEV activates macrophages to secrete proinflammatory cytokines and chemokines, which are dramatically reduced in JEV-infected Clec5a⁻/⁻ macrophages. Although blockade of CLEC5A cannot inhibit JEV infection of neurons and astrocytes, anti-CLEC5A mAb inhibits JEV-induced proinflammatory cytokine release from microglia and prevents bystander damage to neuronal cells. Moreover, JEV causes blood-brain barrier (BBB disintegrity and lethality in STAT1-deficient (Stat1⁻/⁻ mice, whereas peripheral administration of anti-CLEC5A mAb reduces infiltration of virus-harboring leukocytes into the central nervous system (CNS, restores BBB integrity, attenuates neuroinflammation, and protects mice from JEV-induced lethality. Moreover, all surviving mice develop protective humoral and cellular immunity against JEV infection. These observations demonstrate the critical role of CLEC5A in the pathogenesis of Japanese encephalitis, and identify CLEC5A as a target for the development of new treatments to reduce virus-induced brain damage.

  8. Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice.

    Science.gov (United States)

    Spulber, Stefan; Edoff, Karin; Hong, Lie; Morisawa, Shinkatsu; Shirahata, Sanetaka; Ceccatelli, Sandra

    2012-01-01

    Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW) improves the outcome of lipopolysaccharide (LPS)-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p.) or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.

  9. Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice.

    Directory of Open Access Journals (Sweden)

    Stefan Spulber

    Full Text Available Molecular hydrogen has been shown to have neuroprotective effects in mouse models of acute neurodegeneration. The effect was suggested to be mediated by its free-radical scavenger properties. However, it has been shown recently that molecular hydrogen alters gene expression and protein phosphorylation. The aim of this study was to test whether chronic ad libitum consumption of molecular hydrogen-enriched electrochemically reduced water (H-ERW improves the outcome of lipopolysaccharide (LPS-induced neuroinflammation. Seven days after the initiation of H-ERW treatment, C57Bl/6 mice received a single injection of LPS (0.33 mg/kg i.p. or an equivalent volume of vehicle. The LPS-induced sickness behaviour was assessed 2 h after the injection, and recovery was assessed by monitoring the spontaneous locomotor activity in the homecage for 72 h after the administration of LPS. The mice were killed in the acute or recovery phase, and the expression of pro- and antiinflammatory cytokines in the hippocampus was assessed by real-time PCR. We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10. In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation. Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line, suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.

  10. Polymer Claw: Instant Underwater Adhesive

    Science.gov (United States)

    2012-09-24

    3.3 UNDERWATER LAP - SHEAR ADHESION 4 3.4 FULL POLYMER CLAW PROTOTYPE 6 ± NEXT STEPS 7 4.1 BIOFOULED SURFACES 7 4.2 RHEOLOGICAL MEASUREMENTS 7...tested underwater, the lap shear adhesion was ~200x stronger than commercial underwater adhesives after 1 hour. This month also marked the...calibrated to apply a force in the 3.4-3.7 lb. range over a 0.5 sq. in. area. 3.3 Underwater Lap - Shear Adhesion The most important test of the improved

  11. The neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Berezin, V; Bock, E; Poulsen, F M

    2000-01-01

    During the past year, the understanding of the structure and function of neural cell adhesion has advanced considerably. The three-dimensional structures of several of the individual modules of the neural cell adhesion molecule (NCAM) have been determined, as well as the structure of the complex...... between two identical fragments of the NCAM. Also during the past year, a link between homophilic cell adhesion and several signal transduction pathways has been proposed, connecting the event of cell surface adhesion to cellular responses such as neurite outgrowth. Finally, the stimulation of neurite...

  12. TNF-α protein synthesis inhibitor restores neuronal function and reverses cognitive deficits induced by chronic neuroinflammation

    Directory of Open Access Journals (Sweden)

    Belarbi Karim

    2012-01-01

    Full Text Available Abstract Background Chronic neuroinflammation is a hallmark of several neurological disorders associated with cognitive loss. Activated microglia and secreted factors such as tumor necrosis factor (TNF-α are key mediators of neuroinflammation and may contribute to neuronal dysfunction. Our study was aimed to evaluate the therapeutic potential of a novel analog of thalidomide, 3,6'-dithiothalidomide (DT, an agent with anti-TNF-α activity, in a model of chronic neuroinflammation. Methods Lipopolysaccharide or artificial cerebrospinal fluid was infused into the fourth ventricle of three-month-old rats for 28 days. Starting on day 29, animals received daily intraperitoneal injections of DT (56 mg/kg/day or vehicle for 14 days. Thereafter, cognitive function was assessed by novel object recognition, novel place recognition and Morris water maze, and animals were euthanized 25 min following water maze probe test evaluation. Results Chronic LPS-infusion was characterized by increased gene expression of the proinflammatory cytokines TNF-α and IL-1β in the hippocampus. Treatment with DT normalized TNF-α levels back to control levels but not IL-1β. Treatment with DT attenuated the expression of TLR2, TLR4, IRAK1 and Hmgb1, all genes involved in the TLR-mediated signaling pathway associated with classical microglia activation. However DT did not impact the numbers of MHC Class II immunoreactive cells. Chronic neuroinflammation impaired novel place recognition, spatial learning and memory function; but it did not impact novel object recognition. Importantly, treatment with DT restored cognitive function in LPS-infused animals and normalized the fraction of hippocampal neurons expressing the plasticity-related immediate-early gene Arc. Conclusion Our data demonstrate that the TNF-α synthesis inhibitor DT can significantly reverse hippocampus-dependent cognitive deficits induced by chronic neuroinflammation. These results suggest that TNF-α is a

  13. Cannabinoid inhibits HIV-1 Tat-stimulated adhesion of human monocyte-like cells to extracellular matrix proteins

    Science.gov (United States)

    Raborn, Erinn S.; Jamerson, Melissa; Marciano-Cabral, Francine; Cabral, Guy A.

    2014-01-01

    Aims The aim of this study was to assess the effect of select cannabinoids on human immunodeficiency virus type 1 (HIV-1) transactivating (Tat) protein-enhanced monocyte-like cell adhesion to proteins of the extracellular matrix (ECM). Main Methods Collagen IV, laminin, or an ECM gel were used to construct extracellular matrix layers. Human U937 monocyte-like cells were exposed to Tat in the presence of Δ9-tetrahydrocannabinol (THC), CP55,940, and other select cannabinoids. Cell attachment to ECM proteins was assessed using an adhesion assay. Key findings THC and CP55,940 inhibited Tat-enhanced attachment of U937 cells to ECM proteins in a mode that was linked to the cannabinoid receptor type 2 (CB2R). The cannabinoid treatment of Tat-activated U937 cells was associated with altered β1-integrin expression and distribution of polymerized actin, suggesting a modality by which these cannabinoids inhibited adhesion to the ECM. Significance The blood-brain barrier (BBB) is a complex structure that is composed of cellular elements and an extracellular matrix (ECM). HIV-1 Tat promotes transmigration of monocytes across this barrier, a process that includes interaction with ECM proteins. The results indicate that cannabinoids that activate the CB2R inhibit the ECM adhesion process. Thus, this receptor has potential to serve as a therapeutic agent for ablating neuroinflammation associated with HIV-elicited influx of monocytes across the BBB. PMID:24742657

  14. Studies on the Adhesive Property of Snail Adhesive Mucus.

    Science.gov (United States)

    Newar, Janu; Ghatak, Archana

    2015-11-10

    Many gastropod molluscs are known to secrete mucus which allow these animals to adhere to a substrate while foraging over it. While the mucus is known to provide strong adhesion to both dry and wet surfaces, including both horizontal and vertical ones, no systematic study has been carried out to understand the strength of such adhesion under different conditions. We report here results from preliminary studies on adhesion characteristics of the mucus of a snail found in eastern India, Macrochlamys indica. When perturbed, the snail was found to secrete its adhesive mucus, which was collected and subjected to regular adhesion tests. The hydrated mucus was used as such, and also as mixed with buffer of different pH. These experiments suggest that the mucus was slightly alkaline, and showed the maximum adhesion strength of 9 kPa when present in an alkaline buffer. Preliminary studies indicate that adhesive force is related to the ability of the mucus to incorporate water. In alkaline condition, the gel like mass that it forms, incorporate water from a wet surface and enable strong adhesion.

  15. Neuroinflammation and regeneration in the early stages of Alzheimer's disease pathology

    NARCIS (Netherlands)

    Hoozemans, J. J. M.; Veerhuis, R.; Rozemuller, J. M.; Eikelenboom, P.

    2006-01-01

    The initial stages of Alzheimer's disease pathology in the neocortex show upregulation of cell cycle proteins, adhesion and inflammation related factors, indicating the early involvement of inflammatory and regenerating pathways in Alzheimer's disease pathogenesis. These brain changes precede the

  16. Stretchable, Adhesion-Tunable Dry Adhesive by Surface Wrinkling

    KAUST Repository

    Jeong, Hoon Eui

    2010-02-16

    We introduce a simple yet robust method of fabricating a stretchable, adhesion-tunable dry adhesive by combining replica molding and surface wrinkling. By utilizing a thin, wrinkled polydimethyl siloxane (PDMS) sheet with a thickness of 1 mm with built-in micropillars, active, dynamic control of normal and shear adhesion was achieved. Relatively strong normal (∼10.8 N/cm2) and shear adhesion (∼14.7 N/cm2) forces could be obtained for a fully extended (strained) PDMS sheet (prestrain of∼3%), whereas the forces could be rapidly reduced to nearly zero once the prestrain was released (prestrain of ∼0.5%). Moreover, durability tests demonstrated that the adhesion strength in both the normal and shear directions was maintained over more than 100 cycles of attachment and detachment. © 2010 American Chemical Society.

  17. Improved Adhesion and Compliancy of Hierarchical Fibrillar Adhesives.

    Science.gov (United States)

    Li, Yasong; Gates, Byron D; Menon, Carlo

    2015-08-05

    The gecko relies on van der Waals forces to cling onto surfaces with a variety of topography and composition. The hierarchical fibrillar structures on their climbing feet, ranging from mesoscale to nanoscale, are hypothesized to be key elements for the animal to conquer both smooth and rough surfaces. An epoxy-based artificial hierarchical fibrillar adhesive was prepared to study the influence of the hierarchical structures on the properties of a dry adhesive. The presented experiments highlight the advantages of a hierarchical structure despite a reduction of overall density and aspect ratio of nanofibrils. In contrast to an adhesive containing only nanometer-size fibrils, the hierarchical fibrillar adhesives exhibited a higher adhesion force and better compliancy when tested on an identical substrate.

  18. 21 CFR 880.5240 - Medical adhesive tape and adhesive bandage.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Medical adhesive tape and adhesive bandage. 880... Personal Use Therapeutic Devices § 880.5240 Medical adhesive tape and adhesive bandage. (a) Identification. A medical adhesive tape or adhesive bandage is a device intended for medical purposes that consists...

  19. All-trans retinoic acid (ATRA) prevents lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment in aged rats.

    Science.gov (United States)

    Behairi, Nassima; Belkhelfa, Mourad; Rafa, Hayet; Labsi, Moussa; Deghbar, Nahla; Bouzid, Nora; Mesbah-Amroun, Hamida; Touil-Boukoffa, Chafia

    2016-11-15

    We aimed to investigate preventive effects of All-trans retinoic acid (ATRA) on a lipopolysaccharide (LPS)-induced aged neuroinflammation model. We analyzed behavior, systemic nitric oxide (NO) production, cerebral NO synthase (NOS2) and β-amyloid (Aβ) 1-42 expression and tissue integrity in the neuroinflammation model pretreated with ATRA (150μg/ml/rat/day) for 30days. Our results showed that LPS treatment (500μg/kg/day) for 7days disturbed memory, enhanced systemic NO production, NOS2 and Aβ 1-42 cerebral expression and generated an Alzheimer's disease (AD)-like neuronal degeneration. Interestingly, ATRA pretreatment prevented the LPS-induced deleterious effects. ATRA could be a potent preventive approach in AD. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Murine K2P5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K2P3.1- and KV1.3-Dependent Mechanisms

    Directory of Open Access Journals (Sweden)

    Stefan Bittner

    2015-07-01

    Full Text Available Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K2P5.1 (TASK2; KCNK5 channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K2P5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K2P5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K2P5.1 knockout (K2P5.1−/− mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K2P5.1−/− mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K2P3.1 and KV1.3 seems to counterbalance the deletion of K2P5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K2P5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K2P5.1-targeting drugs.

  1. Effect of fibril shape on adhesive properties

    Science.gov (United States)

    Soto, Daniel; Hill, Ginel; Parness, Aaron; Esparza, Noé; Cutkosky, Mark; Kenny, Tom

    2010-08-01

    Research into the gecko's adhesive system revealed a unique architecture for adhesives using tiny hairs. By using a stiff material (β-keratin) to create a highly structured adhesive, the gecko's system demonstrates properties not seen in traditional pressure-sensitive adhesives which use a soft, unstructured planar layer. In contrast to pressure sensitive adhesives, the gecko adhesive displays frictional adhesion, in which increased shear force allows it to withstand higher normal loads. Synthetic fibrillar adhesives have been fabricated but not all demonstrate this frictional adhesion property. Here we report the dual-axis force testing of single silicone rubber pillars from synthetic adhesive arrays. We find that the shape of the adhesive pillar dictates whether frictional adhesion or pressure-sensitive behavior is observed. This work suggests that both types of behavior can be achieved with structures much larger than gecko terminal structures. It also indicates that subtle differences in the shape of these pillars can significantly influence their properties.

  2. Regulative mechanisms of chondrocyte adhesion

    DEFF Research Database (Denmark)

    Schmal, Hagen; Mehlhorn, Alexander T; Fehrenbach, Miriam

    2006-01-01

    Interaction between chondrocytes and extracellular matrix is considered a key factor in the generation of grafts for matrix-associated chondrocyte transplantation. Therefore, our objective was to study the influence of differentiation status on cellular attachment. Adhesion of chondrocytes...... to collagen type II increased after removal from native cartilage up to the third day in monolayer in a dose-dependent manner. Following dedifferentiation after the second passage, adhesion to collagen types I (-84%) and II (-46%) decreased, whereas adhesion to fibrinogen (+59%) and fibronectin (+43......%) increased. A cartilage construct was developed based on a clinically established collagen type I scaffold. In this matrix, more than 80% of the cells could be immobilized by mechanisms of adhesion, filtration, and cell entrapment. Confocal laser microscopy revealed focal adhesion sites as points of cell...

  3. Biological adhesives and fastening devices

    Science.gov (United States)

    Wolpert, H. D.

    2012-04-01

    Sea creatures are a leading source to some of the more interesting discoveries in adhesives. Because sea water naturally breaks down even the strongest conventional adhesive, an alternative is important that could be used in repairing or fabricating anything that might have regular contact with moisture such as: Repairing broken and shattered bones, developing a surgical adhesive, use in the dental work, repairing and building ships, and manufacturing plywood. Some of nature's prototypes include the common mussel, limpet, some bacteria and abalone. As we learn more about these adhesives we are also developing non adhesive fasteners, such as mimicked after studying the octopus, burdock burrs (i.e. Velcro®) and the gecko.

  4. Adhesion testing device

    Science.gov (United States)

    LaPeyronnie, Glenn M. (Inventor); Huff, Charles M. (Inventor)

    2010-01-01

    The present invention provides a testing apparatus and method for testing the adhesion of a coating to a surface. The invention also includes an improved testing button or dolly for use with the testing apparatus and a self aligning button hook or dolly interface on the testing apparatus. According to preferred forms, the apparatus and method of the present invention are simple, portable, battery operated rugged, and inexpensive to manufacture and use, are readily adaptable to a wide variety of uses, and provide effective and accurate testing results. The device includes a linear actuator driven by an electric motor coupled to the actuator through a gearbox and a rotatable shaft. The electronics for the device are contained in the head section of the device. At the contact end of the device, is positioned a self aligning button hook, attached below the load cell located on the actuator shaft.

  5. Dynamics of Nanoparticle Adhesion

    Science.gov (United States)

    Carrillo, J.-M. Y.; Dobrynin, A. V.

    2013-03-01

    We performed molecular dynamics simulations and theoretical analysis of nanoparticle pulling off from adhesive substrates. Our theoretical model of nanoparticle detachment is based on the Kramers solution of the stochastic barrier crossing in effective one dimensional potential well. The activation energy, ΔE , for nanoparticle detachment first decreases linearly with increasing the magnitude of the applied force, f, then it follows a power law ΔE ~(f * - f)3/2 as magnitude of the pulling force f approaches a critical detachment force value, f*. These two different regimes in activation energy dependence on magnitude of the applied force are confirmed by analyzing nanoparticle detachment in effective one dimensional potential obtained by Weighted Histogram Analysis Method. Simulations show that detachment of nanoparticle proceeds through neck formation such that magnitude of the activation energy is determined by balancing surface energy of the neck connecting particle to a substrate with elastic energy of nanoparticle deformation. In this regime the activation energy at zero applied force, ΔE0 , for nanoparticle with radius, Rp, shear modulus, G, surface energy, γp, and work of adhesion, W, is a universal function of the dimensionless parameter δ ~γpW - 2 / 3(GRp)-1/3 . Simulation data are described by a scaling function ΔE0 ~γp5 / 2 Rp1 / 2 G - 3 / 2δ - 3 . 75 . Molecular dynamics simulations of nanoparticle detachment show that the Kramers approach fails in the vicinity of the critical detachment force f* where activation energy barrier becomes smaller than kB T . NSF DMR-1004576

  6. Universal adhesives: the next evolution in adhesive dentistry?

    Science.gov (United States)

    Alex, Gary

    2015-01-01

    Every so often a new material, technique, or technological breakthrough spurs a paradigm shift in the way dentistry is practiced. The development and evolution of reliable enamel and dentin bonding agents is one such example. Indeed, the so-called "cosmetic revolution" in dentistry blossomed in large part due to dramatic advances in adhesive technology. It is the ability to bond various materials in a reasonably predictable fashion to both enamel and dentin substrates that enables dentists to routinely place porcelain veneers, direct and indirect composites, and a plethora of other restorative and esthetic materials. In fact, the longevity and predictability of many (if not most) current restorative procedures is wholly predicated on the dentist's ability to bond various materials to tooth tissues. Adhesive systems have progressed from the largely ineffective systems of the 1970s and early 1980s to the relatively successful total- and self-etching systems of today. The latest players in the adhesive marketplace are the so-called "universal adhesives." In theory, these systems have the potential to significantly simplify and expedite adhesive protocols and may indeed represent the next evolution in adhesive dentistry. But what defines a universal system, and are all these new systems truly "universal" and everything they are claimed to be? This article will examine the origin, chemistry, strengths, weaknesses, and clinical relevance of this new genre of dental adhesives.

  7. The effect of HMGB1 on sub-toxic chlorpyrifos exposure-induced neuroinflammation in amygdala of neonatal rats.

    Science.gov (United States)

    Tian, Jing; Dai, Hongmei; Deng, Yuanying; Zhang, Jie; Li, Ying; Zhou, Jun; Zhao, Mingyi; Zhao, Mengwen; Zhang, Chen; Zhang, Yuxi; Wang, Peipei; Bing, Guoying; Zhao, Lingling

    2015-12-02

    Chlorpyrifos (CPF), one of organophosphorus pesticides (OPs), is associated with developmental neurotoxicity. Inflammatory response is closely related with CPF-induced neurotoxicity. The present study aimed at exploring whether sub-toxic CPF exposure on neonatal rats results in neuroinflammation that mediated by HMGB1/TLR4/NF-κB signaling pathway in the amygdala. The neonatal rats were subcutaneously injected with 5mg/kg CPF for 4 consecutive days (postnatal day 11-14) with or without HMGB1 inhibitor, glycyrrhizin. We assessed the levels of pro-inflammatory cytokines at 12, 24, and 72 h after CPF exposure. The role of HMGB1 on neuroinflammation in sub-toxic exposure during brain development was studied. CPF-treated neonatal rats exhibited a significant increase in the expression of pro-inflammatory cytokines, such as IL-6, TNF-α and HMGB1, and a significant increase in the activation of NF-κB in the amygdala after CPF exposure. Inhibited HMGB1 reduced the release of IL-6 and TNF-α, and inhibited activation of NF-κB. Our findings indicate that CPF exposure on developmental brain might induce the activation of neuroinflammation mediated by HMGB1/TLR4/NF-κB pathway in the amygdala. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Enhanced adhesion by gecko-inspired hierarchical fibrillar adhesives.

    Science.gov (United States)

    Murphy, Michael P; Kim, Seok; Sitti, Metin

    2009-04-01

    The complex structures that allow geckos to repeatably adhere to surfaces consist of multilevel branching fibers with specialized tips. We present a novel technique for fabricating similar multilevel structures from polymer materials and demonstrate the fabrication of arrays of two- and three-level structures, wherein each level terminates in flat mushroom-type tips. Adhesion experiments are conducted on two-level fiber arrays on a 12-mm-diameter glass hemisphere, which exhibit both increased adhesion and interface toughness over one-level fiber samples and unstructured control samples. These adhesion enhancements are the result of increased surface conformation as well as increased extension during detachment.

  9. Rescue from acute neuroinflammation by pharmacological chemokine-mediated deviation of leukocytes

    Directory of Open Access Journals (Sweden)

    Berghmans Nele

    2012-10-01

    Full Text Available Abstract Background Neutrophil influx is an important sign of hyperacute neuroinflammation, whereas the entry of activated lymphocytes into the brain parenchyma is a hallmark of chronic inflammatory processes, as observed in multiple sclerosis (MS and its animal models of experimental autoimmune encephalomyelitis (EAE. Clinically approved or experimental therapies for neuroinflammation act by blocking leukocyte penetration of the blood brain barrier. However, in view of unsatisfactory results and severe side effects, complementary therapies are needed. We have examined the effect of chlorite-oxidized oxyamylose (COAM, a potent antiviral polycarboxylic acid on EAE. Methods EAE was induced in SJL/J mice by immunization with spinal cord homogenate (SCH or in IFN-γ-deficient BALB/c (KO mice with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Mice were treated intraperitoneally (i.p. with COAM or saline at different time points after immunization. Clinical disease and histopathology were compared between both groups. IFN expression was analyzed in COAM-treated MEF cell cultures and in sera and peritoneal fluids of COAM-treated animals by quantitative PCR, ELISA and a bioassay on L929 cells. Populations of immune cell subsets in the periphery and the central nervous system (CNS were quantified at different stages of disease development by flow cytometry and differential cell count analysis. Expression levels of selected chemokine genes in the CNS were determined by quantitative PCR. Results We discovered that COAM (2 mg i.p. per mouse on days 0 and 7 protects significantly against hyperacute SCH-induced EAE in SJL/J mice and MOG35-55-induced EAE in IFN-γ KO mice. COAM deviated leukocyte trafficking from the CNS into the periphery. In the CNS, COAM reduced four-fold the expression levels of the neutrophil CXC chemokines KC/CXCL1 and MIP-2/CXCL2. Whereas the effects of COAM on circulating blood and splenic leukocytes were limited, significant

  10. Neuroinflammation and depression: microglia activation, extracellular microvesicles and microRNA dysregulation

    Directory of Open Access Journals (Sweden)

    Dora eBrites

    2015-12-01

    Full Text Available Patients with chronic inflammation are often associated with the emergence of depression symptoms, while diagnosed depressed patients show increased levels of circulating cytokines. Further studies revealed the activation of the brain immune cell microglia in depressed patients with a greater magnitude in individuals that committed suicide, indicating a crucial role for neuroinflammation in depression brain pathogenesis. Rapid advances in the understanding of microglial and astrocytic neurobiology were obtained in the past fifteen to twenty years. Indeed, recent data reveal that microglia play an important role in managing neuronal cell death, neurogenesis, and synaptic interactions, besides their involvement in immune-response generating cytokines. The communication between microglia and neurons is essential to synchronize these diverse functions with brain activity. Evidence is accumulating that secreted extracellular vesicles (EVs, comprising ectosomes and exosomes with a size ranging from 0.1 to 1 μm, are key players in intercellular signaling. These EVs may carry specific proteins, mRNAs and microRNAs (miRNAs. Transfer of exosomes to neurons was shown to be mediated by oligodendrocytes, microglia and astrocytes that may either be supportive to neurons, or instead disseminate the disease. Interestingly, several recent reports have identified changes in miRNAs in depressed patients, which target not only crucial pathways associated with synaptic plasticity, learning and memory but also the production of neurotrophic factors and immune cell modulation. In this article, we discuss the role of neuroinflammation in the emergence of depression, namely dynamic alterations in the status of microglia response to stimulation, and how their activation phenotypes may have an etiological role in neurodegeneneration, in particular in depressive-like behavior. We will overview the involvement of miRNAs, exosomes, ectosomes and microglia in regulating

  11. Neuroinflammation and tumor necrosis factor signaling in the pathophysiology of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Fiona E McAlpine

    2008-11-01

    Full Text Available Fiona E McAlpine, Malú G TanseyAbstract: Alzheimer’s disease (AD is a progressive neurodegenerative disorder that affects nearly one in two individuals over 90 years of age. Its neuropathological hallmarks are accumulation of extraneuronal plaques of amyloid-beta (Aβ, the presence of neurofibrillary tangles formed by aberrantly hyperphosphorylated tau, progressive synaptic loss, and neurodegeneration which eventually results in decline of memory and cognitive faculties. Although the etiology of sporadic AD in humans is unknown, mutations in amyloid precursor protein or components of its processing machinery (β-secretase and γ-secretase result in overproduction of Aβ1–40 and 1–42 peptides and are sufficient to cause disease. In this review, we highlight the experimental and clinical evidence that suggests a close association between neuroinflammation and AD pathogenesis. Overproduction of inflammatory mediators in the brain occurs when microglia, which are often found in close physical association with amyloid plaques in AD brains, become chronically activated. It has been proposed that elevated levels of pro-inflammatory cytokines, including tumor necrosis factor (TNF, may inhibit phagocytosis of Aβ in AD brains thereby hindering efficient plaque removal by resident microglia. In support of this idea, the bacterial endotoxin lipopolysaccharide, a potent trigger of inflammation that elicits production of TNF and many other cytokines, can accelerate the appearance and severity of AD pathology in several animal models of AD. We review the evidence implicating TNF signaling in AD pathology and discuss how TNF-dependent processes may contribute to cognitive dysfunction and accelerated progression of AD. We conclude by reviewing the observations that provide compelling rationale to investigate the extent to which new therapeutic approaches that selectively target the TNF pathway modify progression of neuropathology in pre-clinical models

  12. Wet adhesion and adhesive locomotion of snails on anti-adhesive non-wetting surfaces.

    Directory of Open Access Journals (Sweden)

    Neil J Shirtcliffe

    Full Text Available Creating surfaces capable of resisting liquid-mediated adhesion is extremely difficult due to the strong capillary forces that exist between surfaces. Land snails use this to adhere to and traverse across almost any type of solid surface of any orientation (horizontal, vertical or inverted, texture (smooth, rough or granular or wetting property (hydrophilic or hydrophobic via a layer of mucus. However, the wetting properties that enable snails to generate strong temporary attachment and the effectiveness of this adhesive locomotion on modern super-slippy superhydrophobic surfaces are unclear. Here we report that snail adhesion overcomes a wide range of these microscale and nanoscale topographically structured non-stick surfaces. For the one surface which we found to be snail resistant, we show that the effect is correlated with the wetting response of the surface to a weak surfactant. Our results elucidate some critical wetting factors for the design of anti-adhesive and bio-adhesion resistant surfaces.

  13. Wet adhesion and adhesive locomotion of snails on anti-adhesive non-wetting surfaces.

    Science.gov (United States)

    Shirtcliffe, Neil J; McHale, Glen; Newton, Michael I

    2012-01-01

    Creating surfaces capable of resisting liquid-mediated adhesion is extremely difficult due to the strong capillary forces that exist between surfaces. Land snails use this to adhere to and traverse across almost any type of solid surface of any orientation (horizontal, vertical or inverted), texture (smooth, rough or granular) or wetting property (hydrophilic or hydrophobic) via a layer of mucus. However, the wetting properties that enable snails to generate strong temporary attachment and the effectiveness of this adhesive locomotion on modern super-slippy superhydrophobic surfaces are unclear. Here we report that snail adhesion overcomes a wide range of these microscale and nanoscale topographically structured non-stick surfaces. For the one surface which we found to be snail resistant, we show that the effect is correlated with the wetting response of the surface to a weak surfactant. Our results elucidate some critical wetting factors for the design of anti-adhesive and bio-adhesion resistant surfaces.

  14. Galectin-1 Reduces Neuroinflammation via Modulation of Nitric Oxide-Arginase Signaling in HIV-1 Transfected Microglia: a Gold Nanoparticle-Galectin-1 "Nanoplex" a Possible Neurotherapeutic?

    Science.gov (United States)

    Aalinkeel, Ravikumar; Mangum, Courtney S; Abou-Jaoude, Eliane; Reynolds, Jessica L; Liu, Maixian; Sundquist, Karin; Parikh, Neil U; Chaves, Lee D; Mammen, Manoj J; Schwartz, Stanley A; Mahajan, Supriya D

    2017-03-01

    Galectins are a family of β-galactoside-binding lectins that are important modulators of homeostasis in the central nervous system (CNS). Galectin-1 is a pivotal regulator of microglia activation that alters the immune balance from neurodegeneration to neuroprotection and could have therapeutic relevance in HIV associated neurocognitive disorders (HAND). We have previously shown that galectin-1 treatment decreased oxidative stress in microglia and hypothesize that the mechanism underlying this phenomenon is the cross regulatory interactions between Nitric oxide (NO) and Arginase I activity in microglia. We induced microglial activation and examined the effect of galectin-1 on the expression of various M1/M2 microglial phenotypic markers. Since, TNF-α is associated with activation of microglial cells involved in pathogenesis of neurodegenerative diseases, we treated HIV transfected human microglial cell cultures (CHME-5/HIV) with TNF-α followed by treatment with galectin-1, to examine the galectin-1 mediated neuro-modulatory response. Our results show that treatment of CHME-5/HIV microglia with galectin-1 reduced TNF-α induced oxidative stress by ~40%, and also significantly reduced iNOS gene expression and NO production while correspondingly increasing arginase-1, cationic amino acid transporter (CAT-1) gene expression and arginase activity. Galectin-1 treatment results in shifting microglia polarization from M1 toward the beneficial M2 phenotype which may prevent neurodegeneration and promote neuroprotection. Thus, our data suggests that galectin-1 treatment reduces neuroinflammation in the CNS microenvironment via the modulation of the NO-arginase network in microglia and thus could play a neuroprotective role in HAND. Further, the therapeutic potential of galectin-1 could be enhanced by conjugation of galectin-1 onto gold nanoparticles (Au-NP), resulting in a nanogold-galectin-1 (Au-Gal-1) multivalent complex that will have more clinical translational

  15. Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology

    Directory of Open Access Journals (Sweden)

    Ferretti Maria

    2012-04-01

    Full Text Available Abstract Background A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated. Methods and results To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway. Conclusions Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology.

  16. Sex-dependent long-term effects of adolescent exposure to THC and/or MDMA on neuroinflammation and serotoninergic and cannabinoid systems in rats.

    Science.gov (United States)

    Lopez-Rodriguez, Ana Belen; Llorente-Berzal, Alvaro; Garcia-Segura, Luis M; Viveros, Maria-Paz

    2014-03-01

    Many young people consume ecstasy as a recreational drug and often in combination with cannabis. In this study, we aimed to mimic human consumption patterns and investigated, in male and female animals, the long-term effects of Δ(9) -tetrahydrocannabinol (THC) and 3,4-methylenedioxymethamphetamine (MDMA) on diverse neuroinflammation and neurotoxic markers. Male and female Wistar rats were chronically treated with increasing doses of THC and/or MDMA during adolescence. The effects of THC and/or MDMA on glial reactivity and on serotoninergic and cannabinoid systems were assessed by immunohistochemistry in the hippocampus and parietal cortex. THC increased the area staining for glial fibrilar acidic protein in both sexes. In males, both drugs, either separately or in combination, increased the proportion of reactive microglia cells [ionized calcium binding adaptor molecule 1 (Iba-1)]. In contrast, in females, each drug, administered alone, decreased of this proportion, whereas the combination of both drugs resulted in a 'normalization' to control values. In males, MDMA reduced the number of SERT positive fibres, THC induced the opposite effect and the group receiving both drugs did not significantly differ from the controls. In females, MDMA reduced the number of SERT positive fibres and the combination of both drugs counteracted this effect. THC also reduced immunostaining for CB1 receptors in females and this effect was aggravated by the combination with MDMA. Adolescent exposure of rats to THC and/or MDMA induced long-term, sex-dependent neurochemical and glial alterations, and revealed interactions between the two drugs. This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6. © 2013 The British Pharmacological Society.

  17. Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer's disease-like amyloid pathology

    Science.gov (United States)

    2012-01-01

    Background A growing body of evidence indicates that inflammation is one of the earliest neuropathological events in Alzheimer's disease. Accordingly, we have recently shown the occurrence of an early, pro-inflammatory reaction in the hippocampus of young, three-month-old transgenic McGill-Thy1-APP mice in the absence of amyloid plaques but associated with intracellular accumulation of amyloid beta petide oligomers. The role of such a pro-inflammatory process in the progression of the pathology remained to be elucidated. Methods and results To clarify this we administered minocycline, a tetracyclic derivative with anti-inflammatory and neuroprotective properties, to young, pre-plaque McGill-Thy1-APP mice for one month. The treatment ended at the age of three months, when the mice were still devoid of plaques. Minocycline treatment corrected the up-regulation of inducible nitric oxide synthase and cyclooxygenase-2 observed in young transgenic placebo mice. Furthermore, the down-regulation of inflammatory markers correlated with a reduction in amyloid precursor protein levels and amyloid precursor protein-related products. Beta-site amyloid precursor protein cleaving enzyme 1 activity and levels were found to be up-regulated in transgenic placebo mice, while minocycline treatment restored these levels to normality. The anti-inflammatory and beta-secretase 1 effects could be partly explained by the inhibition of the nuclear factor kappa B pathway. Conclusions Our study suggests that the pharmacological modulation of neuroinflammation might represent a promising approach for preventing or delaying the development of Alzheimer's disease neuropathology at its initial, pre-clinical stages. The results open new vistas to the interplay between inflammation and amyloid pathology. PMID:22472085

  18. Dual Role of Vitamin C on the Neuroinflammation Mediated Neurodegeneration and Memory Impairments in Colchicine Induced Rat Model of Alzheimer Disease.

    Science.gov (United States)

    Sil, Susmita; Ghosh, Tusharkanti; Gupta, Pritha; Ghosh, Rupsa; Kabir, Syed N; Roy, Avishek

    2016-12-01

    The neurodegeneration in colchicine induced AD rats (cAD) is mediated by cox-2 linked neuroinflammation. The importance of ROS in the inflammatory process in cAD has not been identified, which may be deciphered by blocking oxidative stress in this model by a well-known anti-oxidant vitamin C. Therefore, the present study was designed to investigate the role of vitamin C on colchicine induced oxidative stress linked neuroinflammation mediated neurodegeneration and memory impairments along with peripheral immune responses in cAD. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus of cAD. Administration of vitamin C (200 and 400 mg/kg BW) in cAD resulted in recovery of memory impairments, with prevention of neurodegeneration and neuroinflammation in the hippocampus. The neuroinflammation in the hippocampus also influenced the peripheral immune responses and inflammation in the serum of cAD and all of these parameters were also recovered at 200 and 400 mg dose of vitamin C. However, cAD treated with 600 mg dose did not recover but resulted in increase of memory impairments, neurodegeneration and neuroinflammation in hippocampus along with alteration of peripheral immune responses in comparison to cAD of the present study. Therefore, the present study showed that ROS played an important role in the colchicine induced neuroinflammation linked neurodegeneration and memory impairments along with alteration of peripheral immune responses. It also appears from the results that vitamin C at lower doses showed anti-oxidant effect and at higher dose resulted in pro-oxidant effects in cAD.

  19. Focal Adhesion Kinases in Adhesion Structures and Disease

    Directory of Open Access Journals (Sweden)

    Pierre P. Eleniste

    2012-01-01

    Full Text Available Cell adhesion to the extracellular matrix (ECM is essential for cell migration, proliferation, and embryonic development. Cells can contact the ECM through a wide range of matrix contact structures such as focal adhesions, podosomes, and invadopodia. Although they are different in structural design and basic function, they share common remodeling proteins such as integrins, talin, paxillin, and the tyrosine kinases FAK, Pyk2, and Src. In this paper, we compare and contrast the basic organization and role of focal adhesions, podosomes, and invadopodia in different cells. In addition, we discuss the role of the tyrosine kinases, FAK, Pyk2, and Src, which are critical for the function of the different adhesion structures. Finally, we discuss the essential role of these tyrosine kinases from the perspective of human diseases.

  20. Photovoltaic module with adhesion promoter

    Science.gov (United States)

    Xavier, Grace

    2013-10-08

    Photovoltaic modules with adhesion promoters and methods for fabricating photovoltaic modules with adhesion promoters are described. A photovoltaic module includes a solar cell including a first surface and a second surface, the second surface including a plurality of interspaced back-side contacts. A first glass layer is coupled to the first surface by a first encapsulating layer. A second glass layer is coupled to the second surface by a second encapsulating layer. At least a portion of the second encapsulating layer is bonded directly to the plurality of interspaced back-side contacts by an adhesion promoter.

  1. Structural adhesives directory and databook

    CERN Document Server

    Wilson, Jo

    1996-01-01

    A worldwide directory of commercially available adhesive products for use in a wide range of engineering disciplines. Along with product names and suppliers, basic property data are tabulated and cross-referenced. The book is subdivided according to class of adhesive, with introductions to each class followed by comparison tables and datasheets for each adhesive. The datasheets contain detailed information, from product codes to environmental properties and are therefore of interest across a broad readership. Standardized data will aid the user in cross-comparison between different manufacturers and in easily identifying the required information.

  2. Adhesives from modified soy protein

    Science.gov (United States)

    Sun, Susan [Manhattan, KS; Wang, Donghai [Manhattan, KS; Zhong, Zhikai [Manhattan, KS; Yang, Guang [Shanghai, CN

    2008-08-26

    The present invention provides useful adhesive compositions having similar adhesive properties to conventional UF and PPF resins. The compositions generally include a protein portion and modifying ingredient portion selected from the group consisting of carboxyl-containing compounds, aldehyde-containing compounds, epoxy group-containing compounds, and mixtures thereof. The composition is preferably prepared at a pH level at or near the isoelectric point of the protein. In other preferred forms, the adhesive composition includes a protein portion and a carboxyl-containing group portion.

  3. A local adhesive finger splint.

    Science.gov (United States)

    Macionis, V

    2001-09-01

    A new design of a local static finger splint is proposed. The splint is made by enveloping a length of wire into double-sided adhesive tape. The skin of the region to be immobilized is covered with an adhesive skin dressing, to which the splint is then adhered. This method of attachment gives more freedom in choosing a site of splint application and prevents access obstruction to the wound, blocking of tactile areas, and circulation impairment. The splint is light, low profile, and malleable at ambient temperature. The adhesive splint was used in 5 patients to maintain the first web space open or to immobilize stiff interphalangeal joints in flexion overnight.

  4. Differential effects of duration and age on the consequences of neuroinflammation in the hippocampus.

    Science.gov (United States)

    Bardou, Isabelle; Brothers, Holly M; Kaercher, Roxanne M; Hopp, Sarah C; Wenk, Gary L

    2013-10-01

    The current study investigated the hypothesis that the duration of the proinflammatory environment plays a critical role in the brain's response that results in negative consequences on cognition, biochemistry, and pathology. Lipopolysaccharide or artificial cerebrospinal fluid was slowly (250 ηg/h) infused into the fourth ventricle of young (3-month-old), adult (9-month-old), or aged (23-month-old) male F-344 rats for 21 or 56 days. The rats were then tested in the water pool task and endogenous hippocampal levels of pro- and anti-inflammatory proteins and genes and indicators of glutamatergic function were determined. The duration of the lipopolysaccharide infusion, compared with the age of the rat, had the greatest effect on (1) spatial working memory; (2) the density and distribution of activated microglia within the hippocampus; and (3) the cytokine protein and gene expression profiles within the hippocampus. The duration- and age-dependent consequences of neuroinflammation might explain why human adults respond positively to anti-inflammatory therapies and aged humans do not. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

    Directory of Open Access Journals (Sweden)

    Ilse Bollaerts

    2017-01-01

    Full Text Available Damage to the central nervous system (CNS is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies.

  6. Single-cell profiling reveals GPCR heterogeneity and functional patterning during neuroinflammation.

    Science.gov (United States)

    Tischner, Denise; Grimm, Myriam; Kaur, Harmandeep; Staudenraus, Daniel; Carvalho, Jorge; Looso, Mario; Günther, Stefan; Wanke, Florian; Moos, Sonja; Siller, Nelly; Breuer, Johanna; Schwab, Nicholas; Zipp, Frauke; Waisman, Ari; Kurschus, Florian C; Offermanns, Stefan; Wettschureck, Nina

    2017-08-03

    GPCR expression was intensively studied in bulk cDNA of leukocyte populations, but limited data are available with respect to expression in individual cells. Here, we show a microfluidic-based single-cell GPCR expression analysis in primary T cells, myeloid cells, and endothelial cells under naive conditions and during experimental autoimmune encephalomyelitis, the mouse model of multiple sclerosis. We found that neuroinflammation induces characteristic changes in GPCR heterogeneity and patterning, and we identify various functionally relevant subgroups with specific GPCR profiles among spinal cord-infiltrating CD4 T cells, macrophages, microglia, or endothelial cells. Using GPCRs CXCR4, S1P1, and LPHN2 as examples, we show how this information can be used to develop new strategies for the functional modulation of Th17 cells and activated endothelial cells. Taken together, single-cell GPCR expression analysis identifies functionally relevant subpopulations with specific GPCR repertoires and provides a basis for the development of new therapeutic strategies in immune disorders.

  7. Bioactive phenols as potential neuroinflammation inhibitors from the leaves of Xanthoceras sorbifolia Bunge.

    Science.gov (United States)

    Li, Ning; Wang, Ying; Li, Xuezheng; Zhang, Hong; Zhou, Di; Wang, Wenli; Li, Wei; Zhang, Xiangrong; Li, Xinyu; Hou, Yue; Meng, Dali

    2016-10-15

    Xanthoceras sorbifolia Bunge is a medicinal plant and also a valuable cash crop used for production of edible oil and biofuels in China. In our previous research, systematical phytochemical and bioactive profiles of different parts from X. sorbifolia have been obtained. Here we describe the effective phenols from the leaves of X. sorbifolia, which could function as natural neuroinflammation inhibitors. As a result, 23 compounds were characterized as the phenols from the leaves of X. sorbifolia by means of chromatographical methods and spectroscopic analysis. Among them, flavonoids quercetin3-O-β-d-glucopyarnoside (IC50 13.39±1.27μM), catechin (IC50 9.52±2.18μM), and phenylpropanoids syringaresinol-4-O-β-d-glucopyranoside (IC50 3.08±1.77μM), 4-O-β-d-glucopyranosyl-trans-p-coumaric acid (IC50 9.08±1.23μM) exhibited much stronger inhibiting effect on NO production than that of the positive control minocycline (IC50 37.04±2.09μM) in LPS-induced BV2 cells. Copyright © 2016. Published by Elsevier Ltd.

  8. Bioengineered 3D Glial Cell Culture Systems and Applications for Neurodegeneration and Neuroinflammation.

    Science.gov (United States)

    Watson, P Marc D; Kavanagh, Edel; Allenby, Gary; Vassey, Matthew

    2017-06-01

    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. Given the complexity of the environment from which cells originate, and their various cell-cell and cell-matrix interactions, it is important to develop models that can be controlled and reproducible for drug discovery. 3D cell models have now been developed for almost all CNS cell types, including neurons, astrocytes, microglia, and oligodendrocyte cells. This review will highlight a number of current and emerging techniques for the culture of astrocytes and microglia, glial cell types with a critical role in neurodegenerative and neuroinflammatory conditions. We describe recent advances in glial cell culture using electrospun polymers and hydrogel macromolecules, and highlight how these novel culture environments influence astrocyte and microglial phenotypes in vitro, as compared to traditional 2D systems. These models will be explored to illuminate current trends in the techniques used to create 3D environments for application in research and drug discovery focused on astrocytes and microglial cells.

  9. The Emerging Role of HMGB1 in Neuropathic Pain: A Potential Therapeutic Target for Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Wenbin Wan

    2016-01-01

    Full Text Available Neuropathic pain (NPP is intolerable, persistent, and specific type of long-term pain. It is considered to be a direct consequence of pathological changes affecting the somatosensory system and can be debilitating for affected patients. Despite recent progress and growing interest in understanding the pathogenesis of the disease, NPP still presents a major diagnostic and therapeutic challenge. High mobility group box 1 (HMGB1 mediates inflammatory and immune reactions in nervous system and emerging evidence reveals that HMGB1 plays an essential role in neuroinflammation through receptors such as Toll-like receptors (TLR, receptor for advanced glycation end products (RAGE, C-X-X motif chemokines receptor 4 (CXCR4, and N-methyl-D-aspartate (NMDA receptor. In this review, we present evidence from studies that address the role of HMGB1 in NPP. First, we review studies aimed at determining the role of HMGB1 in NPP and discuss the possible mechanisms underlying HMGB1-mediated NPP progression where receptors for HMGB1 are involved. Then we review studies that address HMGB1 as a potential therapeutic target for NPP.

  10. Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

    Science.gov (United States)

    Nakagawa, Yutaka; Chiba, Kenji

    2016-09-01

    Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  11. A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis.

    Science.gov (United States)

    Granja, Aitor G; Carrillo-Salinas, Francisco; Pagani, Alberto; Gómez-Cañas, María; Negri, Roberto; Navarrete, Carmen; Mecha, Miriam; Mestre, Leyre; Fiebich, Bend L; Cantarero, Irene; Calzado, Marco A; Bellido, Maria L; Fernandez-Ruiz, Javier; Appendino, Giovanni; Guaza, Carmen; Muñoz, Eduardo

    2012-12-01

    Phytocannabinoids like ∆(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms. Natural and synthetic cannabinoids also target the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ), an attractive molecular target for the treatment of neuroinflammation. As part of a study on the SAR of phytocannabinoids, we have investigated the effect of the oxidation modification in the resorcinol moiety of cannabigerol (CBG) on CB(1), CB(2) and PPARγ binding affinities, identifying cannabigerol quinone (VCE-003) as a potent anti-inflammatory agent. VCE-003 protected neuronal cells from excitotoxicity, activated PPARγ transcriptional activity and inhibited the release of pro-inflammatory mediators in LPS-stimulated microglial cells. Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS) was used to investigate the anti-inflammatory activity of this compound in vivo. Motor function performance was evaluated and the neuroinflammatory response and gene expression pattern in brain and spinal cord were studied by immunostaining and qRT-PCR. We found that VCE-003 ameliorated the symptoms associated to TMEV infection, decreased microglia reactivity and modulated the expression of genes involved in MS pathophysiology. These data lead us to consider VCE-003 to have high potential for drug development against MS and perhaps other neuroinflammatory diseases.

  12. A Changing Perspective on the Role of Neuroinflammation in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Donna M. Wilcock

    2012-01-01

    Full Text Available Alzheimer's disease (AD is a complex, neurodegenerative disorder characterized by the presence of amyloid plaques and neurofibrillary tangles in the brain. Glial cells, particularly microglial cells, react to the presence of the amyloid plaques and neurofibrillary tangles producing an inflammatory response. While once considered immunologically privileged due to the blood-brain barrier, it is now understood that the glial cells of the brain are capable of complex inflammatory responses. This paper will discuss the published literature regarding the diverse roles of neuroinflammation in the modulation of AD pathologies. These data will then be related to the well-characterized macrophage phenotypes. The conclusion is that the glial cells of the brain are capable of a host of macrophage responses, termed M1, M2a, M2b, and M2c. The relationship between these states and AD pathologies remains relatively understudied, yet published data using various inflammatory stimuli provides some insight. It appears that an M1-type response lowers amyloid load but exacerbates neurofibrillary tangle pathology. In contrast, M2a is accompanied by elevated amyloid load and appears to ameliorate, somewhat, neurofibrillary pathology. Overall, it is clear that more focused, cause-effect studies need to be performed to better establish how each inflammatory state can modulate the pathologies of AD.

  13. Maternal separation induces neuroinflammation and long-lasting emotional alterations in mice.

    Science.gov (United States)

    Gracia-Rubio, Irene; Moscoso-Castro, Maria; Pozo, Oscar J; Marcos, Josep; Nadal, Roser; Valverde, Olga

    2016-02-04

    Early life experiences play a key role in brain function and behaviour. Adverse events during childhood are therefore a risk factor for psychiatric disease during adulthood, such as mood disorders. Maternal separation is a validated mouse model for maternal neglect, producing negative early life experiences that result in subsequent emotional alteration. Mood disorders have been found to be associated with neurochemical changes and neurotransmitter deficits such as reduced availability of monoamines in discrete brain areas. Emotional alterations like depression result in reduced serotonin availability and enhanced kynurenine metabolism through the action of indoleamine 2, 3-dioxygenase in response to neuroinflammatory factors. This mechanism involves regulation of the neurotransmitter system by neuroinflammatory agents, linking mood regulation to neuroinmunological reactions. In this context, the aim of this study was to investigate the effects of maternal separation with early weaning on emotional behaviour in mice. We investigated neuroinflammatory responses and the state of the tryptophan-kynurenine metabolic pathway in discrete brain areas following maternal separation. We show that adverse events during early life increase risk of long-lasting emotional alterations during adolescence and adulthood. These emotional alterations are particularly severe in females. Behavioural impairments were associated with microglia activation and disturbed tryptophan-kynurenine metabolism in brain areas related to emotional control. This finding supports the preeminent role of neuroinflammation in emotional disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Mitigation of postnatal ethanol-induced neuroinflammation ameliorates trace fear memory deficits in juvenile rats.

    Science.gov (United States)

    Goodfellow, Molly J; Shin, Youn Ju; Lindquist, Derick H

    2018-02-15

    Impairments in behavior and cognition are common in individuals diagnosed with fetal alcohol spectrum disorders (FASD). In this study, FASD model rats were intragastrically intubated with ethanol (5g/kg/day; 5E), sham-intubated (SI), or maintained as naïve controls (NC) over postnatal days (PD) 4-9. Ethanol exposure during this human third trimester-equivalent period induces persistent impairments in hippocampus-dependent learning and memory. The ability of ibuprofen (IBU), a non-steroidal anti-inflammatory drug, to diminish ethanol-induced neuroinflammation and rescue deficits in hippocampus-dependent trace fear conditioning (TFC) was investigated in 5E rats. Phosphate buffered saline vehicle (VEH) or IBU was injected 2h following ethanol exposure over PD4-9, followed by quantification of inflammation-related genes in the dorsal hippocampus of PD10 rats. The 5E-VEH rats exhibited significant increases in Il1b and Tnf, but not Itgam or Gfap, relative to NC, SI-VEH, and 5E-IBU rats. In separate groups of PD31-33 rats, conditioned fear (freezing) was significantly reduced in 5E-VEH rats during TFC testing, but not acquisition, compared to SI-VEH and, critically, 5E-IBU rats. Results suggest neuroimmune activation in response to ethanol within the neonate hippocampus contributes to later-life cognitive dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Differential effects of duration and age upon the consequences of neuroinflammation in the hippocampus

    Science.gov (United States)

    Bardou, Isabelle; Brothers, Holly M.; Kaercher, Roxanne M.; Hopp, Sarah C.; Wenk, Gary L.

    2013-01-01

    The current study investigated the hypothesis that the duration of the pro-inflammatory environment plays a critical role in the brain’s response that result in negative consequences upon cognition, biochemistry and pathology. Lipopolysaccharide (LPS) or aCSF was slowly (250 ηg/hr) infused into the IVth ventricle of young (3 mo), adult (9 mo) or aged (23 mo) male F-344 rats for 21 or 56 days. The rats were then tested in the water pool task and endogenous hippocampal levels of pro- and anti-inflammatory proteins and genes as well as indicators of glutamatergic function were determined. The duration of the LPS infusion, as compared to the age of the rat, had the greatest impact upon 1) spatial working memory, 2) the density and distribution of activated microglia within the hippocampus, and 3) the cytokine protein and gene expression profiles within the hippocampus. The duration- and age-dependent consequences of neuroinflammation may explain why adult humans respond positively to anti-inflammatory therapies while aged humans do not. PMID:23639208

  16. Efficacy of vitamin D in treating multiple sclerosis-like neuroinflammation depends on developmental stage.

    Science.gov (United States)

    Adzemovic, Milena Z; Zeitelhofer, Manuel; Hochmeister, Sonja; Gustafsson, Sven A; Jagodic, Maja

    2013-11-01

    The association of vitamin D deficiency with higher prevalence, relapse rate and progression of multiple sclerosis (MS) has stimulated great interest in using vitamin D supplementation as a preventative measure and even a therapy for established MS. However, there is a considerable lack of evidence when it comes to an age/developmental stage-dependent efficacy of vitamin D action and a time-window for the most effective prophylactic treatment remains unclear. We studied the effect of vitamin D supplementation in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), an animal model of MS, at three different developmental stages in rats. Supplementation treatment was initiated: i) prior to gestation and maintained throughout pre- and early postnatal development (gestation and lactation); ii) after weaning, throughout juvenile/adolescence period and iii) in adult age. We observed a marked attenuation of EAE in juvenile/adolescent rats reflected in a less severe CNS inflammation and demyelination, accompanied by a lower amount of IFN-γ producing MOG-specific T cells. Moreover, the cytokine expression pattern in these rats reflected a more anti-inflammatory phenotype of their peripheral immune response. However, the same supplementation regimen failed to improve the disease outcome both in adult rats and in rats treated during pre- and early post-natal development. Our data demonstrate a developmental stage-dependent efficiency of vitamin D to ameliorate neuroinflammation, suggesting that childhood and adolescence should be the target for the most effective preventive treatment. © 2013.

  17. Naringin Attenuates Autophagic Stress and Neuroinflammation in Kainic Acid-Treated Hippocampus In Vivo

    Directory of Open Access Journals (Sweden)

    Kyoung Hoon Jeong

    2015-01-01

    Full Text Available Kainic acid (KA is well known as a chemical compound to study epileptic seizures and neuronal excitotoxicity. KA-induced excitotoxicity causes neuronal death by induction of autophagic stress and microglia-derived neuroinflammation, suggesting that the control of KA-induced effects may be important to inhibit epileptic seizures with neuroprotection. Naringin, a flavonoid in grapefruit and citrus fruits, has anti-inflammatory and antioxidative activities, resulting in neuroprotection in animal models from neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. In the present study, we examined its beneficial effects involved in antiautophagic stress and antineuroinflammation in the KA-treated hippocampus. Our results showed that naringin treatment delayed the onset of KA-induced seizures and decreased the occurrence of chronic spontaneous recurrent seizures (SRS in KA-treated mice. Moreover, naringin treatment protected hippocampal CA1 neurons in the KA-treated hippocampus, ameliorated KA-induced autophagic stress, confirmed by the expression of microtubule-associated protein light chain 3 (LC3, and attenuated an increase in tumor necrosis factor-α (TNFα in activated microglia. These results suggest that naringin may have beneficial effects of preventing epileptic events and neuronal death through antiautophagic stress and antineuroinflammation in the hippocampus in vivo.

  18. The resolution of neuroinflammation in neurodegeneration: leukocyte recruitment via the choroid plexus.

    Science.gov (United States)

    Schwartz, Michal; Baruch, Kuti

    2014-01-07

    Inflammation is an integral part of the body's physiological repair mechanism, unless it remains unresolved and becomes pathological, as evident in the progressive nature of neurodegeneration. Based on studies from outside the central nervous system (CNS), it is now understood that the resolution of inflammation is an active process, which is dependent on well-orchestrated innate and adaptive immune responses. Due to the immunologically privileged status of the CNS, such resolution mechanism has been mostly ignored. Here, we discuss resolution of neuroinflammation as a process that depends on a network of immune cells operating in a tightly regulated sequence, involving the brain's choroid plexus (CP), a unique neuro-immunological interface, positioned to integrate signals it receives from the CNS parenchyma with signals coming from circulating immune cells, and to function as an on-alert gate for selective recruitment of inflammation-resolving leukocytes to the inflamed CNS parenchyma. Finally, we propose that functional dysregulation of the CP reflects a common underlying mechanism in the pathophysiology of neurodegenerative diseases, and can thus serve as a potential novel target for therapy.

  19. Role of neuroinflammation in the emotional and cognitive alterations displayed by animal models of obesity

    Directory of Open Access Journals (Sweden)

    Nathalie eCastanon

    2015-07-01

    Full Text Available Obesity is associated with a high prevalence of mood disorders and cognitive dysfunctions in addition to being a significant risk factor for important health complications such as cardiovascular diseases and type 2 diabetes. Identifying the pathophysiological mechanisms underlying these health issues is a major public health challenge. Based on recent findings, from studies conducted on animal models of obesity, it has been proposed that inflammatory processes may participate in both the peripheral and brain disorders associated with the obesity condition including the development of emotional and cognitive alterations. This is supported by the fact that obesity is characterized by peripheral low-grade inflammation, originating from increased adipose tissue mass and/or dysbiosis (changes in gut microbiota environment, both of which contribute to increased susceptibility to immune-mediated diseases. In this review, we provide converging evidence showing that obesity is associated with exacerbated neuroinflammation leading to dysfunction in vulnerable brain regions associated with mood regulation, learning and memory such as the hippocampus. These findings give new insights to the pathophysiological mechanisms contributing to the development of brain disorders in the context of obesity and provide valuable data for introducing new therapeutic strategies for the treatment of neuropsychiatric complications often reported in obese patients.

  20. Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

    Directory of Open Access Journals (Sweden)

    Mariana Raineri

    Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

  1. [Realgar is active ingredient of Angong Niuhuang pill in protection against LPS-induced neuroinflammation].

    Science.gov (United States)

    Zhang, Feng; Lu, Yuanfu; Liu, Jie; Shi, Jingshan

    2010-12-01

    To determine the effects of Angong Niuhuang pill (AGNHW) on lipopolysaccharide (LPS)-induced neuroinflammation and further to investigate the role of realgar and cinnabar on AGNHW-mediated neuroprotection. Primary rat midbrain neuron-glia cultures were used as an in vitro model to examine the effects of AGNHW on LPS-induced dopamine (DA) neuronal damage. Cultures were divided randomly into five groups: control, LPS, LPS plus AGNHW, LPS plus realgar and LPS plus cinnabar. Dopaminergic neurotoxicity was measured by [3H] DA uptake assay. The production of intracellular reactive oxygen species (ROS) was quantified via the DCFH-DA probe. Real-time RT-PCR was applied to detect the mRNA expression of pro-inflammatory factors. Then the protein levels of these factors were determined by ELISA and western blot assay. Compared with the control group, LPS apparently decreased DA uptake capacity (P realgar significantly inhibited LPS-induced reduction of DA uptake (P realgar is one of active components for AGNHW to produce anti-inflammatory effects.

  2. Neuroinflammation as Fuel for Axonal Regeneration in the Injured Vertebrate Central Nervous System

    Science.gov (United States)

    Van houcke, Jessie

    2017-01-01

    Damage to the central nervous system (CNS) is one of the leading causes of morbidity and mortality in elderly, as repair after lesions or neurodegenerative disease usually fails because of the limited capacity of CNS regeneration. The causes underlying this limited regenerative potential are multifactorial, but one critical aspect is neuroinflammation. Although classically considered as harmful, it is now becoming increasingly clear that inflammation can also promote regeneration, if the appropriate context is provided. Here, we review the current knowledge on how acute inflammation is intertwined with axonal regeneration, an important component of CNS repair. After optic nerve or spinal cord injury, inflammatory stimulation and/or modification greatly improve the regenerative outcome in rodents. Moreover, the hypothesis of a beneficial role of inflammation is further supported by evidence from adult zebrafish, which possess the remarkable capability to repair CNS lesions and even restore functionality. Lastly, we shed light on the impact of aging processes on the regenerative capacity in the CNS of mammals and zebrafish. As aging not only affects the CNS, but also the immune system, the regeneration potential is expected to further decline in aged individuals, an element that should definitely be considered in the search for novel therapeutic strategies. PMID:28203046

  3. The Transcription Factor IRF8 Activates Integrin-mediated TGFβ Signaling and Promotes Neuroinflammation

    Science.gov (United States)

    Yoshida, Yuko; Yoshimi, Ryusuke; Yoshii, Hiroaki; Kim, Daniel; Dey, Anup; Xiong, Huabao; Munasinghe, Jeeva; Yazawa, Itaru; O’Donovan, Michael J.; Maximova, Olga A.; Sharma, Suveena; Zhu, Jinfang; Wang, Hongsheng; Morse, Herbert C.; Ozato, Keiko

    2014-01-01

    SUMMARY Recent epidemiological studies have identified interferon regulatory factor 8 (IRF8) as a susceptibility factor for multiple sclerosis (MS). However, how IRF8 influences the neuroinflammatory disease has remained unknown. By studying the role of IRF8 in experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, we found that Irf8−/− mice are resistant to EAE. Furthermore, expression of IRF8 in antigen presenting cells (APCs, such as macrophages, dendritic cells and microglia), but not in T cells, facilitated disease onset and progression through multiple pathways. IRF8 enhanced αvβ8 integrin expression in APCs and activated TGFβ signaling leading to T helper 17 (Th17) cell differentiation. IRF8 induced a cytokine milieu that favored growth and maintenance of Th1 and Th17 cells, by stimulating interleukin-12 (IL12) and IL23 production, but inhibiting IL27 during EAE. Finally, IRF8 activated microglia and exacerbated neuroinflammation. Together, this work provides mechanistic bases by which IRF8 contributes to the pathogenesis of MS. PMID:24485804

  4. Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model

    Directory of Open Access Journals (Sweden)

    Constantino Tomas-Sanchez

    2016-01-01

    Full Text Available Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p. for 14 days before common carotid artery occlusion (CCAO in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.

  5. Modafinil Abrogates Methamphetamine-Induced Neuroinflammation and Apoptotic Effects in the Mouse Striatum

    Science.gov (United States)

    Goitia, Belen; Garcia-Rill, Edgar; Krasnova, Irina N.; Cadet, Jean Lud; Urbano, Francisco J.; Bisagno, Veronica

    2012-01-01

    Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4×5 mg/kg, i.p., 2 h apart) and modafinil co-administration (2×90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections) on glial cells (microglia and astroglia). We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum. PMID:23056363

  6. Bacterial endotoxin adhesion to different types of orthodontic adhesives

    Directory of Open Access Journals (Sweden)

    Priscilla Coutinho ROMUALDO

    Full Text Available Abstract Bacterial endotoxin (LPS adhesion to orthodontic brackets is a known contributing factor to inflammation of the adjacent gingival tissues. Objective The aim of this study was to assess whether LPS adheres to orthodontic adhesive systems, comparing two commercial brands. Material and Methods Forty specimens were fabricated from Transbond XT and Light Bond composite and bonding agent components (n=10/component, then contaminated by immersion in a bacterial endotoxin solution. Contaminated and non-contaminated acrylic resin samples were used as positive and negative control groups, respectively. LPS quantification was performed by the Limulus Amebocyte Lysate QCL-1000™ test. Data obtained were scored and subjected to the Chi-square test using a significance level of 5%. Results There was endotoxin adhesion to all materials (p0.05. There was no significant difference (p>0.05 among commercial brands. Affinity of endotoxin was significantly greater for the bonding agents (p=0.0025. Conclusions LPS adhered to both orthodontic adhesive systems. Regardless of the brand, the endotoxin had higher affinity for the bonding agents than for the composites. There is no previous study assessing the affinity of LPS for orthodontic adhesive systems. This study revealed that LPS adheres to orthodontic adhesive systems. Therefore, additional care is recommended to orthodontic applications of these materials.

  7. Adhesive capsulitis: a review.

    Science.gov (United States)

    Ewald, Anthony

    2011-02-15

    Adhesive capsulitis is a common, yet poorly understood, condition causing pain and loss of range of motion in the shoulder. It can occur in isolation or concomitantly with other shoulder conditions (e.g., rotator cuff tendinopathy, bursitis) or diabetes mellitus. It is often self-limited, but can persist for years and may never fully resolve. The diagnosis is usually clinical, although imaging can help rule out other conditions. The differential diagnosis includes acromioclavicular arthropathy, autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis), biceps tendinopathy, glenohumeral osteoarthritis, neoplasm, rotator cuff tendinopathy or tear (with or without impingement), and subacromial and subdeltoid bursitis. Several treatment options are commonly used, but few have high-level evidence to support them. Because the condition is often self-limited, observation and reassurance may be considered; however, this may not be acceptable to many patients because of the painful and debilitating nature of the condition. Nonsurgical treatments include analgesics (e.g., acetaminophen, nonsteroidal anti-inflammatory drugs), oral prednisone, and intra-articular corticosteroid injections. Home exercise regimens and physical therapy are often prescribed. Surgical treatments include manipulation of the joint under anesthesia and capsular release.

  8. Allergic Stomatitis From Orthodontic Adhesives.

    Science.gov (United States)

    Peterson, Mark R; Wong, Priscilla H; Dickson, Scott D; Coop, Christopher A

    2017-03-01

    We report a case of a type IV hypersensitivity reaction causing oral stomatitis, presumed to be the result of common dental adhesives. The case was diagnosed using patch testing to the dental adhesives that were used in the patient. Both of the adhesives tested contained a form of acrylate that is being seen more frequently in the literature as a cause of type IV hypersensitivity reactions. Metals can cause allergic reactions; however, other contact items need to be considered as a cause of oral allergic reactions. Cases of allergic stomatitis are rising and there is question if all-in-one adhesives may be contributing to this rise. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

  9. 21 CFR 878.4010 - Tissue adhesive.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tissue adhesive. 878.4010 Section 878.4010 Food... DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4010 Tissue adhesive. (a) Tissue adhesive for the topical approximation of skin—(1) Identification. A tissue adhesive for the topical...

  10. An Overview of Dental Adhesive Systems and the Dynamic Tooth-Adhesive Interface.

    Science.gov (United States)

    Bedran-Russo, Ana; Leme-Kraus, Ariene A; Vidal, Cristina M P; Teixeira, Erica C

    2017-10-01

    From the conception of resin-enamel adhesion to today's contemporary dental adhesive systems, clinicians are no longer afraid of exploring the many advantages brought by adhesive restorative concepts. To maximize the performance of adhesive-based restorative procedures, practitioners must be familiar with the mechanism of adhesion, clinical indications, proper handling, the inherent limitations of the materials and the biological challenges. This review provides an overview of the current status of restorative dental adhesives, their mechanism of adhesion, mechanisms of degradation of dental adhesive interfaces, how to maximize performance, and future trends in adhesive dentistry. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Fibrillar Adhesive for Climbing Robots

    Science.gov (United States)

    Pamess, Aaron; White, Victor E.

    2013-01-01

    A climbing robot needs to use its adhesive patches over and over again as it scales a slope. Replacing the adhesive at each step is generally impractical. If the adhesive or attachment mechanism cannot be used repeatedly, then the robot must carry an extra load of this adhesive to apply a fresh layer with each move. Common failure modes include tearing, contamination by dirt, plastic deformation of fibers, and damage from loading/ unloading. A gecko-like fibrillar adhesive has been developed that has been shown useful for climbing robots, and may later prove useful for grasping, anchoring, and medical applications. The material consists of a hierarchical fibrillar structure that currently contains two levels, but may be extended to three or four levels in continuing work. The contacting level has tens of thousands of microscopic fibers made from a rubberlike material that bend over and create intimate contact with a surface to achieve maximum van der Waals forces. By maximizing the real area of contact that these fibers make and minimizing the bending energy necessary to achieve that contact, the net amount of adhesion has been improved dramatically.

  12. Curcumin attenuates beta-amyloid-induced neuroinflammation via activation of peroxisome proliferator-activated receptor-gamma function in a rat model of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Zun-Jing Liu

    2016-08-01

    Full Text Available Neuroinflammation is known to have a pivotal role in the pathogenesis of Alzheimer’s disease (AD, and curcumin has been reported to have therapeutical effects on AD because of its anti-inflammatory effects. Curcumin is not only a potent PPARγ agonist, but also has neuroprotective effects on cerebral ischemic injury. However, whether PPARγ activated by curcumin is responsible for the anti-neuroinflammation and neuroprotection on AD remains unclear, and needs to be further investigated. Here, using both APP/PS1 transgenic mice and beta-amyloid-induced neuroinflammation in mixed neuronal/glial cultures, we showed that curcumin significantly alleviated spatial memory deficits in APP/PS1 mice and promoted cholinergic neuronal function in vivo and in vitro. Curcumin also reduced the activation of microglia and astrocytes, as well as cytokine production and inhibited nuclear factor kappa B (NF-κB signaling pathway, suggesting the beneficial effects of curcumin on AD are attributable to the suppression of neuroinflammation. Attenuation of these beneficial effects occurred when co-administrated with PPARγ antagonist GW9662 or silence of PPARγ gene expression, indicating that PPARγ might be involved in anti-inflammatory effects. Circular dichroism and co-immunoprecipitation analysis showed that curcumin directly bound to PPARγ and increased the transcriptional activity and protein levels of PPARγ. Taking together, these data suggested that PPARγ might be a potential target of curcumin, acting to alleviate neuroinflammation and improve neuronal function in AD.

  13. Proteomic dataset of the sea urchin Paracentrotus lividus adhesive organs and secreted adhesive

    NARCIS (Netherlands)

    Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

    Sea urchins have specialized adhesive organs called tube feet, which mediate strong but reversible adhesion. Tube feet are composed by a disc, producing adhesive and de-adhesive secretions for substratum attachment, and a stem for movement. After detachment the secreted adhesive remains bound to the

  14. Cell adhesion assay to determine the interaction between NGL-3 with LAR cell adhesion molecules

    OpenAIRE

    sprotocols

    2015-01-01

    In the cell adhesion assay, two groups of cells expressing different cell adhesion molecules are mixed together to determine whether the adhesion molecules can interact with each other and whether their interaction mediates cell adhesion. We used this assay to determine the interaction of NGL-3 with other synaptic cell adhesion molecules including LAR.

  15. Influence of substrate modulus on gecko adhesion

    OpenAIRE

    Klittich, Mena R.; Wilson, Michael C.; Craig Bernard; Rochelle M. Rodrigo; Austin J. Keith; Niewiarowski, Peter H.; Ali Dhinojwala

    2017-01-01

    The gecko adhesion system fascinates biologists and materials scientists alike for its strong, reversible, glue-free, dry adhesion. Understanding the adhesion system?s performance on various surfaces can give clues as to gecko behaviour, as well as towards designing synthetic adhesive mimics. Geckos encounter a variety of surfaces in their natural habitats; tropical geckos, such as Gekko gecko, encounter hard, rough tree trunks as well as soft, flexible leaves. While gecko adhesion on hard su...

  16. Early Minocycline and Late FK506 Treatment Improves Survival and Alleviates Neuroinflammation, Neurodegeneration, and Behavioral Deficits in Prion-Infected Hamsters.

    Science.gov (United States)

    Shah, Syed Zahid Ali; Zhao, Deming; Taglialatela, Giulio; Khan, Sher Hayat; Hussain, Tariq; Dong, Haodi; Lai, Mengyu; Zhou, Xiangmei; Yang, Lifeng

    2017-04-01

    Prion infections of the central nervous system (CNS) are characterized by initial reactive gliosis followed by overt neuronal death. Gliosis is likely to be caused initially by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrPSc) of the normal cellular prion protein (PrPc) in the brain. Proinflammatory cytokines and chemokines released by PrPSc-activated glia and stressed neurons may also contribute directly or indirectly to the disease development by enhancing gliosis and inducing neurotoxicity. Recent studies have illustrated that early neuroinflammation activates nuclear factor of activated T cells (NFAT) in the calcineurin signaling cascade, resulting in nuclear translocation of nuclear factor kappa B (NF-κB) to promote apoptosis. Hence, useful therapeutic approaches to slow down the course of prion disease development should control early inflammatory responses to suppress NFAT signaling. Here we used a hamster model of prion diseases to test, for the first time, the neuroprotective and NFAT-suppressive effect of a second-generation semisynthetic tetracycline derivative, minocycline, versus a calcineurin inhibitor, FK506, with known NFAT suppressive activity. Our results indicate that prolonged treatment with minocycline, starting from the presymptomatic stage of prion disease was more effective than FK506 given either during the presymptomatic or symptomatic stage of prion disease. Specifically, minocycline treatment reduced the expression of the astrocyte activation marker glial fibrillary acidic protein and of the microglial activation marker ionized calcium-binding adapter molecule-1, subsequently reducing the level of proinflammatory cytokines interleukin 1β and tumor necrosis factor-α. We further found that minocycline and FK506 treatment inhibited mitogen-activated protein kinase p38 phosphorylation and NF-κB nuclear translocation in a caspase-dependent manner, and enhanced phosphorylated cyclic adenosine monophosphate

  17. Amyloid precursor protein metabolism and inflammation markers in preclinical Alzheimer disease.

    Science.gov (United States)

    Alcolea, Daniel; Martínez-Lage, Pablo; Sánchez-Juan, Pascual; Olazarán, Javier; Antúnez, Carmen; Izagirre, Andrea; Ecay-Torres, Mirian; Estanga, Ainara; Clerigué, Montserrat; Guisasola, Maria Concepción; Sánchez Ruiz, Domingo; Marín Muñoz, Juan; Calero, Miguel; Blesa, Rafael; Clarimón, Jordi; Carmona-Iragui, María; Morenas-Rodríguez, Estrella; Rodríguez-Rodríguez, Eloy; Vázquez Higuera, José Luis; Fortea, Juan; Lleó, Alberto

    2015-08-18

    To investigate CSF markers involved in amyloid precursor protein processing, neuronal damage, and neuroinflammation in the preclinical stages of Alzheimer disease (AD) and participants with suspected non-Alzheimer pathology (SNAP). We collected CSF from 266 cognitively normal volunteers participating in a cross-sectional multicenter study (the SIGNAL study) to investigate markers involved in amyloid precursor protein processing (Aβ42, sAPPβ, β-secretase activity), neuronal damage (total-tau [t-tau], phospho-tau [p-tau]), and neuroinflammation (YKL-40). We analyzed the relationship among biomarkers, clinical variables, and the APOE genotype, and compared biomarker levels across the preclinical stages of the National Institute on Aging-Alzheimer's Association classification: stage 0, 1, 2, 3, and SNAP. The median age in the whole cohort was 58.8 years (range 39.8-81.6). Participants in stages 2-3 and SNAP had higher levels of YKL-40 than those in stages 0 and 1. Participants with SNAP had higher levels of sAPPβ than participants in stage 0 and 1. No differences were found between stages 0, 1, and 2-3 in sAPPβ and β-secretase activity in CSF. Age correlated with t-tau, p-tau, and YKL-40. It also correlated with Aβ42, but only in APOE ε4 carriers. Aβ42 correlated positively with t-tau, sAPPβ, and YKL-40 in participants with normal Aβ42. Our findings suggest that inflammation in the CNS increases in normal aging and is intimately related to markers of neurodegeneration in the preclinical stages of AD and SNAP. sAPPβ and β-secretase activity are not useful diagnostic or staging markers in preclinical AD. © 2015 American Academy of Neurology.

  18. Established and emerging biological activity markers of inflammatory bowel disease

    DEFF Research Database (Denmark)

    Nielsen, O H; Vainer, B; Madsen, S M

    2000-01-01

    orosomucoid and CRP), leukocyte and platelet counts, albumin, neopterin, and beta2-microglobulin will be reviewed together with emerging disease markers such as antibodies of the ANCA/ASCA type, cytokines (e.g., IL-1, IL-2Ralpha, IL-6, IL-8, TNF-alpha, and TNF-alpha receptors) and with various adhesion......Assessment of disease activity in inflammatory bowel disease (IBD), i.e., ulcerative colitis (UC) and Crohn's disease (CD), is done using clinical parameters and various biological disease markers. Ideally, a disease marker must: be able to identify individuals at risk of a given disorder......, be disease specific, mirror the disease activity and, finally, be easily applicable for routine clinical purposes. However, no such disease markers have yet been identified for IBD. In this article, classical disease markers including erythrocyte sedimentation rate, acute phase proteins (especially...

  19. Optimizing Adhesive Design by Understanding Compliance.

    Science.gov (United States)

    King, Daniel R; Crosby, Alfred J

    2015-12-23

    Adhesives have long been designed around a trade-off between adhesive strength and releasability. Geckos are of interest because they are the largest organisms which are able to climb utilizing adhesive toepads, yet can controllably release from surfaces and perform this action over and over again. Attempting to replicate the hierarchical, nanoscopic features which cover their toepads has been the primary focus of the adhesives field until recently. A new approach based on a scaling relation which states that reversible adhesive force capacity scales with (A/C)(1/2), where A is the area of contact and C is the compliance of the adhesive, has enabled the creation of high strength, reversible adhesives without requiring high aspect ratio, fibrillar features. Here we introduce an equation to calculate the compliance of adhesives, and utilize this equation to predict the shear adhesive force capacity of the adhesive based on the material components and geometric properties. Using this equation, we have investigated important geometric parameters which control force capacity and have shown that by controlling adhesive shape, adhesive force capacity can be increased by over 50% without varying pad size. Furthermore, we have demonstrated that compliance of the adhesive far from the interface still influences shear adhesive force capacity. Utilizing this equation will allow for the production of adhesives which are optimized for specific applications in commercial and industrial settings.

  20. Dual Targeting of Amyloid-beta Clearance and Neuroinflammation as a Novel Therapeutic Approach against Alzheimer's Disease

    Science.gov (United States)

    Batarseh, Yazan S.

    Amyloid-beta (Abeta) cascade hypothesis suggests that Alzheimer's disease (AD) is related to an imbalance between the production and clearance of Abeta peptide. Sporadic AD has been related to faulty clearance of Abeta. Accumulation of Abeta oligomers (Abetao) has been linked to several downstream toxic effects including neuroinflammation, synaptic loss, and cellular death. Abeta transport across the blood-brain barrier (BBB) is one of the primary pathways for reducing Abeta load in the brain, which work hand in hand with other parenchymal mechanisms to reduce Abeta levels including intra and extracellular degradation by a family of Abeta degrading enzymes. Established AD drugs, such as the cholinesterase inhibitor donepezil, have been reported to have several additional non-cholinergic effects that alter Abeta pathology; reduce Abeta load, anti-inflammatory response, and attenuate synaptic loss. However, their limited effect only lead to minor improvements in AD symptoms without improving the prognosis of the disease. The lack of effective medical treatment for AD led to several studies focusing on establishing new therapeutic approaches to reduce Abeta pathology. We aimed to identify and characterize natural products that are capable of enhancing the BBB clearance of Abeta in addition to reducing neuroinflammation. Our first project was to investigate the role of oleocanthal (one of the active ingredients in extra-virgin olive oil; EVOO) on attenuating Abeta toxic effects on neurons and astrocytes. We developed Abeta oligomers (Abetao) induced inflammatory environment by exposing neurons and astrocytes to accumulative doses of Abetao to investigate oleocanthal effect on modulating Abetao pathological changes in neurons and astrocytes. Our findings demonstrated oleocanthal prevented Abetao-induced synaptic proteins, SNAP-25 and PSD-95, down-regulation in neurons, attenuated Abetao-induced inflammation, and restored glutamine transporter (GLT1) and glucose

  1. Influence of adhesive application methods and rebonding agent application on sealing effectiveness of all-in-one self-etching adhesives.

    Science.gov (United States)

    Demirci, Mustafa; Tuncer, Safa; Tekçe, Neslihan; Erdilek, Dina; Uysal, Ömer

    2013-10-01

    The choice of adhesive application methods could affect the microleakage of self-etch adhesives. To evaluate the effect of acid-etching, doubling adhesive application time, doubling adhesive coating, and rebonding agent application on microleakage of self-etch adhesives in Class V cavities. Seventy human third molars with Class V cavities assigned to five groups according to different adhesive application protocols for the three dentin adhesives (Clearfil S3 Bond, Kuraray Medical, Okayama, Japan; Optibond All-in-One, Kerr Corporation Orange, CA, USA; G-Aenial Bond, GC Corporation, Tokyo, Japan): group 1, manufacturer's recommendations; group 2, prior acid-etching of cavities; group 3, double application time; group 4, two consecutive coats of the adhesives; group 5, rebonding application on restoration margins. After bonding, the cavities were filled with a resin composite (Filtek Supreme XT, 3M ESPE Dental Products, St. Paul, MN, USA). The teeth were thermocycled, and the specimens were examined for microleakage using methylene blue as a marker. For Clearfil S3 Bond and Optibond All-in-One, microleakage in groups 2 and 5 were significantly lower than other groups' enamel margins. In groups 1, 2, 4, and 5, Clearfil S3 Bond exhibited significantly more leakage than the other dentin bonding agents in dentin margins. Microleakage was significantly higher on dentinal margins compared with the enamel margins for Clearfil S3 Bond in all of the groups. Optibond All-in-One showed significantly lower microleakage in dentin margins in all groups except groups 2 and 5. Acid-etching usually promoted the reduction of microleakage in enamel margins. On the other hand, rebonding application usually contributed to the reduction of microleakage more than other methods in enamel and dentin margins. Acid-etching or rebonding application may contribute to reduction of microleakage of all-in-one self-etching adhesives. © 2013 Wiley Periodicals, Inc.

  2. Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Monica R P Elmore

    Full Text Available Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg or phosphate buffered saline (PBS was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR, as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function

  3. Sex Bias in Pathogenesis of Autoimmune Neuroinflammation: Relevance for Dimethyl Fumarate Immunomodulatory/Anti-oxidant Action.

    Science.gov (United States)

    Stojić-Vukanić, Zorica; Kotur-Stevuljević, Jelena; Nacka-Aleksić, Mirjana; Kosec, Duško; Vujnović, Ivana; Pilipović, Ivan; Dimitrijević, Mirjana; Leposavić, Gordana

    2017-05-22

    In the present study, upon showing sexual dimorphism in dimethyl fumarate (DMF) efficacy to moderate the clinical severity of experimental autoimmune encephalomyelitis (EAE) in Dark Agouti rats, cellular and molecular substrate of this dimorphism was explored. In rats of both sexes, DMF administration from the day of immunization attenuated EAE severity, but this effect was more prominent in males leading to loss of the sexual dimorphism observed in vehicle-administered controls. Consistently, in male rats, DMF was more efficient in diminishing the number of CD4+ T lymphocytes infiltrating spinal cord (SC) and their reactivation, the number of IL-17+ T lymphocytes and particularly cellularity of their highly pathogenic IFN-γ+GM-CSF+IL-17+ subset. This was linked with changes in SC CD11b+CD45+TCRαβ- microglia/proinflammatory monocyte progeny, substantiated in a more prominent increase in the frequency of anti-inflammatory phygocyting CD163+ cells and the cells expressing high surface levels of immunoregulatory CD83 molecule (associated with apoptotic cells phagocytosis and implicated in downregulation of CD4+ T lymphocyte reactivation) among CD11b+CD45+TCRαβ- cells in male rat SC. These changes were associated with greater increase in the nuclear factor (erythroid-derived 2)-like 2 expression in male rats administered with DMF. In accordance with the previous findings, DMF diminished reactive nitrogen and oxygen species generation and consistently, SC level of advanced oxidation protein products, to the greater extent in male rats. Overall, our study indicates sex-specificity in the sensitivity of DMF cellular and molecular targets and encourages sex-based clinical research to define significance of sex for action of therapeutic agents moderating autoimmune neuroinflammation-/oxidative stress-related nervous tissue damage.

  4. Dimethyl fumarate attenuates neuroinflammation and neurobehavioral deficits induced by experimental traumatic brain injury.

    Science.gov (United States)

    Casili, Giovanna; Campolo, Michela; Paterniti, Irene; Lanza, Marika; Filippone, Alessia; Cuzzocrea, Salvatore; Esposito, Emanuela

    2018-01-23

    TBI is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in preclinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI). Mice were orally administered with DMF at the doses of 1, 10 and 30 mg/Kg, 1h and 4h after CCI. We performed histological, molecular, and immunohistochemistry analysis on the traumatic penumbral areas of the brain 24 hours after CCI. DMF treatment notably reduced histological damage and behavioral impairments, reducing neurodegeneration as evidenced by assessments of neuronal loss, Fluoro-jade C and TUNEL staining; also, treatment with DMF blocked apoptosis process increasing B-cell lymphoma 2 (Bcl-2) expression in injured cortex. Furthermore, DMF treatment up-regulated antioxidant Kelch-like ECH-associated protein 1/ Nuclear factor erythroid 2- related factor (Keap-1/Nrf-2) pathway, inducing activation of manganese superoxide dismutase (Mn-SOD) and heme-oxygenase-1 (HO-1) and reducing 4-hydroxy-2-nonenal (4-HNE) staining. Also, regulating NF-κB pathway, DMF treatment decreased the severity of inflammation through a modulation of neuronal nitrite oxide synthase (nNOS), interleukin 1 (Il-1β), tumor necrosis factor (TNF-α), cyclooxygenase 2 (COX-2) and myeloperoxidase (MPO) activity, reducing ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Our results support the thesis that DMF may be an effective neuroprotectant after brain trauma and warrants further study.

  5. TREM2 deficiency attenuates neuroinflammation and protects against neurodegeneration in a mouse model of tauopathy.

    Science.gov (United States)

    Leyns, Cheryl E G; Ulrich, Jason D; Finn, Mary B; Stewart, Floy R; Koscal, Lauren J; Remolina Serrano, Javier; Robinson, Grace O; Anderson, Elise; Colonna, Marco; Holtzman, David M

    2017-10-24

    Variants in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) were recently found to increase the risk for developing Alzheimer's disease (AD). In the brain, TREM2 is predominately expressed on microglia, and its association with AD adds to increasing evidence implicating a role for the innate immune system in AD initiation and progression. Thus far, studies have found TREM2 is protective in the response to amyloid pathology while variants leading to a loss of TREM2 function impair microglial signaling and are deleterious. However, the potential role of TREM2 in the context of tau pathology has not yet been characterized. In this study, we crossed Trem2(+/+) (T2(+/+)) and Trem2(-/-) (T2(-/-)) mice to the PS19 human tau transgenic line (PS) to investigate whether loss of TREM2 function affected tau pathology, the microglial response to tau pathology, or neurodegeneration. Strikingly, by 9 mo of age, T2(-/-)PS mice exhibited significantly less brain atrophy as quantified by ventricular enlargement and preserved cortical volume in the entorhinal and piriform regions compared with T2(+/+)PS mice. However, no TREM2-dependent differences were observed for phosphorylated tau staining or insoluble tau levels. Rather, T2(-/-)PS mice exhibited significantly reduced microgliosis in the hippocampus and piriform cortex compared with T2(+/+)PS mice. Gene expression analyses and immunostaining revealed microglial activation was significantly attenuated in T2(-/-)PS mice, and there were lower levels of inflammatory cytokines and astrogliosis. These unexpected findings suggest that impairing microglial TREM2 signaling reduces neuroinflammation and is protective against neurodegeneration in the setting of pure tauopathy. Copyright © 2017 the Author(s). Published by PNAS.

  6. Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

    Directory of Open Access Journals (Sweden)

    Chung-Hsi Hsing

    2015-01-01

    Full Text Available Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs modulate cytokine synthesis and release. Trichostatin A (TSA, an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS- induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p. injected with vehicle or TSA (0.3 mg/kg. One hour later, they were injected (i.p. with saline or Escherichia coli LPS (1 mg/kg. We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO, TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression.

  7. Environmental enrichment attenuates hippocampal neuroinflammation and improves cognitive function during influenza infection

    Science.gov (United States)

    Jurgens, Heidi A.; Johnson, Rodney W.

    2012-01-01

    Recent findings from our lab have shown that peripheral infection of adult mice with influenza A/PR/8/34 (H1N1) virus induces a neuroinflammatory response that is paralleled by loss of neurotrophic and glial regulatory factors in the hippocampus, and deficits in cognitive function. Environmental enrichment has been shown to exert beneficial effects on the brain and behavior in many central nervous system (CNS) disorders, but its therapeutic potential during peripheral viral infection remains unknown. Therefore, the objective of the present study was to determine if long-term continuous exposure to environmental enrichment could prevent and/or attenuate the negative effects of influenza infection on the hippocampus and spatial cognition. Mice were housed in enriched or standard conditions for 4 months, and continued to live in their respective environments throughout influenza infection. Cognitive function was assessed in a reversal learning version of the Morris water maze, and changes in hippocampal expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α, IFN-α), neurotrophic (BDNF, NGF), and immunomodulatory (CD200, CX3CL1) factors were determined. We found that environmental enrichment reduced neuroinflammation and helped prevent the influenza-induced reduction in hippocampal CD200. These changes were paralleled by improved cognitive performance of enriched mice infected with influenza when compared to infected mice in standard housing conditions. Collectively, these data are the first to demonstrate the positive impact of environmental enrichment on the brain and cognition during peripheral viral infection, and suggest that enhanced modulation of the neuroimmune response may underlie these beneficial effects. PMID:22687335

  8. Changes in brain oxysterols at different stages of Alzheimer's disease: Their involvement in neuroinflammation

    Directory of Open Access Journals (Sweden)

    Gabriella Testa

    2016-12-01

    Full Text Available Alzheimer's disease (AD is a gradually debilitating disease that leads to dementia. The molecular mechanisms underlying AD are still not clear, and at present no reliable biomarkers are available for the early diagnosis. In the last several years, together with oxidative stress and neuroinflammation, altered cholesterol metabolism in the brain has become increasingly implicated in AD progression. A significant body of evidence indicates that oxidized cholesterol, in the form of oxysterols, is one of the main triggers of AD. The oxysterols potentially most closely involved in the pathogenesis of AD are 24-hydroxycholesterol and 27-hydroxycholesterol, respectively deriving from cholesterol oxidation by the enzymes CYP46A1 and CYP27A1. However, the possible involvement of oxysterols resulting from cholesterol autooxidation, including 7-ketocholesterol and 7β-hydroxycholesterol, is now emerging. In a systematic analysis of oxysterols in post-mortem human AD brains, classified by the Braak staging system of neurofibrillary pathology, alongside the two oxysterols of enzymatic origin, a variety of oxysterols deriving from cholesterol autoxidation were identified; these included 7-ketocholesterol, 7α-hydroxycholesterol, 4β-hydroxycholesterol, 5α,6α-epoxycholesterol, and 5β,6β-epoxycholesterol. Their levels were quantified and compared across the disease stages. Some inflammatory mediators, and the proteolytic enzyme matrix metalloprotease-9, were also found to be enhanced in the brains, depending on disease progression. This highlights the pathogenic association between the trends of inflammatory molecules and oxysterol levels during the evolution of AD. Conversely, sirtuin 1, an enzyme that regulates several pathways involved in the anti-inflammatory response, was reduced markedly with the progression of AD, supporting the hypothesis that the loss of sirtuin 1 might play a key role in AD. Taken together, these results strongly support the

  9. CXCL13 is the major determinant for B cell recruitment to the CSF during neuroinflammation

    Directory of Open Access Journals (Sweden)

    Kowarik Markus C

    2012-05-01

    Full Text Available Abstract Background The chemokines and cytokines CXCL13, CXCL12, CCL19, CCL21, BAFF and APRIL are believed to play a role in the recruitment of B cells to the central nervous system (CNS compartment during neuroinflammation. To determine which chemokines/cytokines show the strongest association with a humoral immune response in the cerebrospinal fluid (CSF, we measured their concentrations in the CSF and correlated them with immune cell subsets and antibody levels. Methods Cytokine/chemokine concentrations were measured in CSF and serum by ELISA in patients with non-inflammatory neurological diseases (NIND, n = 20, clinically isolated syndrome (CIS, n = 30, multiple sclerosis (MS, n = 20, Lyme neuroborreliosis (LNB, n = 8 and patients with other inflammatory neurological diseases (OIND, n = 30. Albumin, IgG, IgA and IgM were measured by nephelometry. CSF immune cell subsets were determined by seven-color flow cytometry. Results CXCL13 was significantly elevated in the CSF of all patient groups with inflammatory diseases. BAFF levels were significantly increased in patients with LNB and OIND. CXCL12 was significantly elevated in patients with LNB. B cells and plasmablasts were significantly elevated in the CSF of all patients with inflammatory diseases. CXCL13 showed the most consistent correlation with CSF B cells, plasmablasts and intrathecal Ig synthesis. Conclusions CXCL13 seems to be the major determinant for B cell recruitment to the CNS compartment in different neuroinflammatory diseases. Thus, elevated CSF CXCL13 levels rather reflect a strong humoral immune response in the CNS compartment than being specific for a particular disease entity.

  10. Characterizing newly repopulated microglia in the adult mouse: impacts on animal behavior, cell morphology, and neuroinflammation.

    Science.gov (United States)

    Elmore, Monica R P; Lee, Rafael J; West, Brian L; Green, Kim N

    2015-01-01

    Microglia are the primary immune cell in the brain and are postulated to play important roles outside of immunity. Administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor, PLX3397, to adult mice results in the elimination of ~99% of microglia, which remain eliminated for as long as treatment continues. Upon removal of the inhibitor, microglia rapidly repopulate the entire adult brain, stemming from a central nervous system (CNS) resident progenitor cell. Using this method of microglial elimination and repopulation, the role of microglia in both healthy and diseased states can be explored. Here, we examine the responsiveness of newly repopulated microglia to an inflammatory stimulus, as well as determine the impact of these cells on behavior, cognition, and neuroinflammation. Two month-old wild-type mice were placed on either control or PLX3397 diet for 21 d to eliminate microglia. PLX3397 diet was then removed in a subset of animals to allow microglia to repopulate and behavioral testing conducted beginning at 14 d repopulation. Finally, inflammatory profiling of the microglia-repopulated brain in response to lipopolysaccharide (LPS; 0.25 mg/kg) or phosphate buffered saline (PBS) was determined 21 d after inhibitor removal using quantitative real time polymerase chain reaction (RT-PCR), as well as detailed analyses of microglial morphologies. We find mice with repopulated microglia to perform similarly to controls by measures of behavior, cognition, and motor function. Compared to control/resident microglia, repopulated microglia had larger cell bodies and less complex branching in their processes, which resolved over time after inhibitor removal. Inflammatory profiling revealed that the mRNA gene expression of repopulated microglia was similar to normal resident microglia and that these new cells appear functional and responsive to LPS. Overall, these data demonstrate that newly repopulated microglia function similarly to the

  11. Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.

    Science.gov (United States)

    Norden, Diana M; Bicer, Sabahattin; Clark, Yvonne; Jing, Runfeng; Henry, Christopher J; Wold, Loren E; Reiser, Peter J; Godbout, Jonathan P; McCarthy, Donna O

    2015-01-01

    Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1β mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1β in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Transplantation of Cerebral Dopamine Neurotrophic Factor Transducted BMSCs in Contusion Spinal Cord Injury of Rats: Promotion of Nerve Regeneration by Alleviating Neuroinflammation.

    Science.gov (United States)

    Zhao, Hua; Cheng, Lei; Du, Xinwen; Hou, Yong; Liu, Yi; Cui, Zhaoqiang; Nie, Lin

    2016-01-01

    Traumatic spinal cord injury (SCI) causes neuron death and axonal damage resulting in functional motor and sensory loss, showing limited regeneration because of adverse microenvironment such as neuroinflammation and glial scarring. Currently, there is no effective therapy to treat SCI in clinical practice. Bone marrow-derived mesenchymal stem cells (BMSCs) are candidates for cell therapies but its effect is limited by neuroinflammation and adverse microenvironment in the injured spinal cord. In this study, we developed transgenic BMSCs overexpressing cerebral dopamine neurotrophic factor (CDNF), a secretory neurotrophic factor that showed potent effects on neuron protection, anti-inflammation, and sciatic nerve regeneration in previous studies. Our results showed that the transplantation of CDNF-BMSCs suppressed neuroinflammation and decreased the production of proinflammatory cytokines after SCI, resulting in the promotion of locomotor function and nerve regeneration of the injured spinal cord. This study presents a novel promising strategy for the treatment of spinal cord injury.

  13. Attenuation of melanoma invasion by a secreted variant of activated leukocyte cell adhesion molecule.

    NARCIS (Netherlands)

    Kilsdonk, J.W.J. van; Wilting, R.H.; Bergers, M.; Muijen, G.N.P. van; Schalkwijk, J.; Kempen, L.C.L.T. van; Swart, G.W.M.

    2008-01-01

    Activated leukocyte cell adhesion molecule (ALCAM/CD166/MEMD), a marker of various cancers and mesenchymal stem cells, is involved in melanoma metastasis. We have exploited a secreted NH(2)-terminal fragment, sALCAM, to test the hypothesis that ALCAM coordinates tissue growth and cell migration.

  14. Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration

    Directory of Open Access Journals (Sweden)

    Maria Emilia Figueiredo-Pereira

    2015-01-01

    Full Text Available The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia and prion diseases. Cyclooxygenases (COX -1 and COX-2, which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1 exert their actions, (2 potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3 disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4 contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury, and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects.

  15. Innovative Electrostatic Adhesion Technologies

    Science.gov (United States)

    Bryan, Tom; Macleod, Todd; Gagliano, Larry; Williams, Scott; McCoy, Brian

    2015-01-01

    Developing specialized Electro-Static grippers (commercially used in Semiconductor Manufacturing and in package handling) will allow gentle and secure Capture, Soft Docking, and Handling of a wide variety of materials and shapes (such as upper-stages, satellites, arrays, and possibly asteroids) without requiring physical features or cavities for a pincher or probe or using harpoons or nets. Combined with new rigid boom mechanisms or small agile chaser vehicles, flexible, high speed Electro-Static Grippers can enable compliant capture of spinning objects starting from a safe stand-off distance. Electroadhesion (EA) can enable lightweight, ultra-low-power, compliant attachment in space by using an electrostatic force to adhere similar and dissimilar surfaces. A typical EA enabled device is composed of compliant space-rated materials, such as copper-clad polyimide encapsulated by polymers. Attachment is induced by strong electrostatic forces between any substrate material, such as an exterior satellite panel and a compliant EA gripper pad surface. When alternate positive and negative charges are induced in adjacent planar electrodes in an EA surface, the electric fields set up opposite charges on the substrate and cause an electrostatic adhesion between the electrodes and the induced charges on the substrate. Since the electrodes and the polymer are compliant and can conform to uneven or rough surfaces, the electrodes can remain intimately close to the entire surface, enabling high clamping pressures. Clamping pressures of more than 3 N/cm2 in shear can be achieved on a variety of substrates with ultra-low holding power consumption (measured values are less than 20 microW/Newton weight held). A single EA surface geometry can be used to clamp both dielectric and conductive substrates, with slightly different physical mechanisms. Furthermore EA clamping requires no normal force be placed on the substrate, as conventional docking requires. Internally funded research and

  16. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1β expression in a rat model of neuroinflammation

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    Soliman Mahmoud L

    2012-03-01

    Full Text Available Abstract Background Long-term acetate supplementation reduces neuroglial activation and cholinergic cell loss in a rat model of lipopolysaccharide-induced neuroinflammation. Additionally, a single dose of glyceryl triacetate, used to induce acetate supplementation, increases histone H3 and H4 acetylation and inhibits histone deacetylase activity and histone deacetylase-2 expression in normal rat brain. Here, we propose that the therapeutic effect of acetate in reducing neuroglial activation is due to a reversal of lipopolysaccharide-induced changes in histone acetylation and pro-inflammatory cytokine expression. Methods In this study, we examined the effect of a 28-day-dosing regimen of glyceryl triacetate, to induce acetate supplementation, on brain histone acetylation and interleukin-1β expression in a rat model of lipopolysaccharide-induced neuroinflammation. The effect was analyzed using Western blot analysis, quantitative real-time polymerase chain reaction and enzymic histone deacetylase and histone acetyltransferase assays. Statistical analysis was performed using one-way analysis of variance, parametric or nonparametric when appropriate, followed by Tukey's or Dunn's post-hoc test, respectively. Results We found that long-term acetate supplementation increased the proportion of brain histone H3 acetylated at lysine 9 (H3K9, histone H4 acetylated at lysine 8 and histone H4 acetylated at lysine 16. However, unlike a single dose of glyceryl triacetate, long-term treatment increased histone acetyltransferase activity and had no effect on histone deacetylase activity, with variable effects on brain histone deacetylase class I and II expression. In agreement with this hypothesis, neuroinflammation reduced the proportion of brain H3K9 acetylation by 50%, which was effectively reversed with acetate supplementation. Further, in rats subjected to lipopolysaccharide-induced neuroinflammation, the pro-inflammatory cytokine interleukin-1β protein

  17. Bile Acid-Mediated Sphingosine-1-Phosphate Receptor 2 Signaling Promotes Neuroinflammation during Hepatic Encephalopathy in Mice

    Directory of Open Access Journals (Sweden)

    Matthew McMillin

    2017-07-01

    Full Text Available Hepatic encephalopathy (HE is a neuropsychiatric complication that occurs due to deteriorating hepatic function and this syndrome influences patient quality of life, clinical management strategies and survival. During acute liver failure, circulating bile acids increase due to a disruption of the enterohepatic circulation. We previously identified that bile acid-mediated signaling occurs in the brain during HE and contributes to cognitive impairment. However, the influences of bile acids and their downstream signaling pathways on HE-induced neuroinflammation have not been assessed. Conjugated bile acids, such as taurocholic acid (TCA, can activate sphingosine-1-phosphate receptor 2 (S1PR2, which has been shown to promote immune cell infiltration and inflammation in other models. The current study aimed to assess the role of bile-acid mediated S1PR2 signaling in neuroinflammation and disease progression during azoxymethane (AOM-induced HE in mice. Our findings demonstrate a temporal increase of bile acids in the cortex during AOM-induced HE and identified that cortical bile acids were elevated as an early event in this model. In order to classify the specific bile acids that were elevated during HE, a metabolic screen was performed and this assay identified that TCA was increased in the serum and cortex during AOM-induced HE. To reduce bile acid concentrations in the brain, mice were fed a diet supplemented with cholestyramine, which alleviated neuroinflammation by reducing proinflammatory cytokine expression in the cortex compared to the control diet-fed AOM-treated mice. S1PR2 was expressed primarily in neurons and TCA treatment increased chemokine ligand 2 mRNA expression in these cells. The infusion of JTE-013, a S1PR2 antagonist, into the lateral ventricle prior to AOM injection protected against neurological decline and reduced neuroinflammation compared to DMSO-infused AOM-treated mice. Together, this identifies that reducing bile acid

  18. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    DEFF Research Database (Denmark)

    Mottahedin, Amin; Ardalan, Maryam; Chumak, Tetyana

    2017-01-01

    The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly...... physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following...

  19. Increasing extracellular cGMP in cerebellum in vivo reduces neuroinflammation, GABAergic tone and motor in-coordination in hyperammonemic rats.

    Science.gov (United States)

    Cabrera-Pastor, Andrea; Balzano, Tiziano; Hernández-Rabaza, Vicente; Malaguarnera, Michele; Llansola, Marta; Felipo, Vicente

    2017-12-27

    Hyperammonemia is a main contributor to cognitive impairment and motor in-coordination in patients with hepatic encephalopathy. Hyperammonemia-induced neuroinflammation mediates the neurological alterations in hepatic encephalopathy. Intracerebral administration of extracellular cGMP restores some but not all types of cognitive impairment. Motor in-coordination, is mainly due to increased GABAergic tone in cerebellum. We hypothesized that extracellular cGMP would restore motor coordination in hyperammonemic rats by normalizing GABAergic tone in cerebellum and that this would be mediated by reduction of neuroinflammation. The aims of this work were to assess whether chronic intracerebral administration of cGMP to hyperammonemic rats: 1) restores motor coordination; 2) reduces neuroinflammation in cerebellum; 3) reduces extracellular GABA levels and GABAergic tone in cerebellum; and also 4) to provide some advance in the understanding on the molecular mechanisms involved. The results reported show that rats with chronic hyperammonemia show neuroinflammation in cerebellum, including microglia and astrocytes activation and increased levels of IL-1b and TNFa and increased membrane expression of the TNFa receptor. This is associated with increased glutaminase expression and extracellular glutamate, increased amount of the GABA transporter GAT-3 in activated astrocytes, increased extracellular GABA in cerebellum and motor in-coordination. Chronic intracerebral administration of extracellular cGMP to rats with chronic hyperammonemia reduces neuroinflammation, including microglia and astrocytes activation and membrane expression of the TNFa receptor. This is associated with reduced nuclear NF-κB, glutaminase expression and extracellular glutamate, reduced amount of the GABA transporter GAT-3 in activated astrocytes and reduced extracellular GABA in cerebellum and restoration of motor coordination. The data support that extracellular cGMP restores motor coordination in

  20. CD11c(hi) Dendritic Cells Regulate Ly-6C(hi) Monocyte Differentiation to Preserve Immune-privileged CNS in Lethal Neuroinflammation.

    Science.gov (United States)

    Kim, Jin Hyoung; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Patil, Ajit Mahadev; Han, Young Woo; Park, Sang-Youel; Lee, John Hwa; Kim, Koanhoi; Eo, Seong Kug

    2015-12-02

    Although the roles of dendritic cells (DCs) in adaptive defense have been defined well, the contribution of DCs to T cell-independent innate defense and subsequent neuroimmunopathology in immune-privileged CNS upon infection with neurotropic viruses has not been completely defined. Notably, DC roles in regulating innate CD11b(+)Ly-6C(hi) monocyte functions during neuroinflammation have not yet been addressed. Using selective ablation of CD11c(hi)PDCA-1(int/lo) DCs without alteration in CD11c(int)PDCA-1(hi) plasmacytoid DC number, we found that CD11c(hi) DCs are essential to control neuroinflammation caused by infection with neurotropic Japanese encephalitis virus, through early and increased infiltration of CD11b(+)Ly-6C(hi) monocytes and higher expression of CC chemokines. More interestingly, selective CD11c(hi) DC ablation provided altered differentiation and function of infiltrated CD11b(+)Ly-6C(hi) monocytes in the CNS through Flt3-L and GM-CSF, which was closely associated with severely enhanced neuroinflammation. Furthermore, CD11b(+)Ly-6C(hi) monocytes generated in CD11c(hi) DC-ablated environment had a deleterious rather than protective role during neuroinflammation, and were more quickly recruited into inflamed CNS, depending on CCR2, thereby exacerbating neuroinflammation via enhanced supply of virus from the periphery. Therefore, our data demonstrate that CD11c(hi) DCs provide a critical and unexpected role to preserve the immune-privileged CNS in lethal neuroinflammation via regulating the differentiation, function, and trafficking of CD11b(+)Ly-6C(hi) monocytes.

  1. Adhesion of Blended Polymer Films.

    Science.gov (United States)

    Staszel, Christopher; Sinha-Ray, Suman; Yarin, Alexander L.; Pourdeyhimi, Behnam

    The adhesive energy of blended and monolithic PCL and PCL-N6 surfaces was measured by blister method and linked to the surface composition of the blended samples. It was shown that PCL does not adhere to N6 after heat-treatment at 55 C, while the monolithic PCL films adhered to the blended samples solely via the PCL islands at the surface. The surface concentration of PCL in the blended samples was established using the novel staining method. It was shown that the surface concentration of PCL differs from its bulk content in the blended samples. The measurements also revealed that the surface concentration of PCL is practically linearly proportionality to the normalized adhesion energy between the blended PCL-N6 samples and monolithic PCL films. Several statistical characteristics of the surfaces of the blended samples were used to characterize their uniformity/non-uniformity. It was shown that increasing the surface uniformity of the adhering component in the blended samples (PCL), one increases the adhesion energy. Moreover, at about 70% of PCL at the surface, the adhesion energy of blended samples to monolithic PCL films could reach the value characterization of the adhesion between two monolithic PCL samples. This work is supported by the Nonwovens Institute, Grant No. 14-163.

  2. Polyurethane adhesives in flat roofs

    Directory of Open Access Journals (Sweden)

    Bogárová Markéta

    2017-01-01

    Full Text Available It is necessary to stabilize individual layers of flat roofs, mainly because of wind suction. Apart from anchoring and surcharge, these layers can be secured by bonding. At present gluing is an indispensable and widely used stabilization method. On our market we can found many types of adhesives, most widely used are based on polyurethane. This paper focuses on problematic about stabilization thermal insulation from expanded polystyrene to vapor barrier from bitumen. One of the main issues is to calculate the exact amount of adhesive, which is required to guarantee the resistance against wind suction. In this problematic we can not find help neither in technical data sheets provided by the manufactures. Some of these data sheets contain at least information about amount of adhesive depending on location in roof plane and building height, but they do not specify the strength of such connection. It was therefore resorted to select several representatives polyurethane adhesives and their subsequent testing on specimens simulating the flat roof segment. The paper described the test methodology and results for two types of polyurethane adhesives.

  3. Adhesive polymer films for the prevention of postsurgical adhesions

    OpenAIRE

    Esser, Eva

    2017-01-01

    Current clinically used lipophilic anti-adhesive films, like SurgiWrap®, have to be fixed to the affected tissue using sutures due to their limited adhesiveness and only degrade very slowly within months and years due to the hydrophobicity and the high molecular weight of the used PLA, which effectively inhibits the uptake of water. The aim of this work was to prepare films that have a much faster degradation pathway due to a hydrogel nature and ideally adhere to the tissue by themselves. The...

  4. Lignin-Furfural Based Adhesives

    Directory of Open Access Journals (Sweden)

    Prajakta Dongre

    2015-07-01

    Full Text Available Lignin recovered from the hot-water extract of sugar maple (Acer saccharum is used in this study to synthesize adhesive blends to replace phenol-formaldehyde (PF resin. Untreated lignin is characterized by lignin content and nuclear magnetic resonance (NMR analysis. The molecular weight distribution of the lignin and the blends are characterized by size exclusion chromatography (SEC. The effect of pH (0.3, 0.65 and 1, ex situ furfural, and curing conditions on the tensile properties of adhesive reinforced glass fibers is determined and compared to the reinforcement level of commercially available PF resin. The adhesive blend prepared at pH = 0.65 with no added furfural exhibits the highest tensile properties and meets 90% of the PF tensile strength.

  5. Integrin-Matrix Clusters Form Podosome-like Adhesions in the Absence of Traction Forces

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    Cheng-han Yu

    2013-12-01

    Full Text Available Matrix-activated integrins can form different adhesion structures. We report that nontransformed fibroblasts develop podosome-like adhesions when spread on fluid Arg-Gly-Asp peptide (RGD-lipid surfaces, whereas they habitually form focal adhesions on rigid RGD glass surfaces. Similar to classic macrophage podosomes, the podosome-like adhesions are protrusive and characterized by doughnut-shaped RGD rings that surround characteristic core components including F-actin, N-WASP, and Arp2/Arp3. Furthermore, there are 18 podosome markers in these adhesions, though they lack matrix metalloproteinases that characterize invadopodia and podosomes of Src-transformed cells. When nontransformed cells develop force on integrin-RGD clusters by pulling RGD lipids to prefabricated rigid barriers (metal lines spaced by 1–2 μm, these podosomes fail to form and instead form focal adhesions. The formation of podosomes on fluid surfaces is mediated by local activation of phosphoinositide 3-kinase (PI3K and the production of phosphatidylinositol-(3,4,5-triphosphate (PIP3 in a FAK/PYK2-dependent manner. Enrichment of PIP3 precedes N-WASP activation and the recruitment of RhoA-GAP ARAP3. We propose that adhesion structures can be modulated by traction force development and that production of PIP3 stimulates podosome formation and subsequent RhoA downregulation in the absence of traction force.

  6. Adhesion dynamics for cellulose nanocomposites.

    Science.gov (United States)

    Nordgren, Niklas; Lönnberg, Hanna; Hult, Anders; Malmström, Eva; Rutland, Mark W

    2009-10-01

    The efficiency of poly(ε-caprolactone) (PCL) as a matrix polymer for cellulose nanocomposites has been investigated at the macromolecular contact level using atomic force microscopy in a colloidal probe configuration. Model cellulose microspheres grafted with PCL were prepared via ring-opening polymerization. Force measurements between the functionalized particles revealed the adhesion to be highly dependent on the contact time because of a diffusion-controlled mechanism. Moreover, an increase of the temperature to 60 degrees C (close to T(m) for the PCL graft) greatly enhanced the adhesion at the polymer-polymer interface, demonstrating the importance of entanglements in the annealing of composite materials.

  7. Adhesion complex formation after small keratectomy wounds in the cornea.

    Science.gov (United States)

    Stock, E L; Kurpakus, M A; Sambol, B; Jones, J C

    1992-02-01

    The adhesion complex of the corneal epithelium consists of the hemidesmosome and its associated structures, such as anchoring filaments, lamina densa of the basement membrane, and anchoring fibrils. It contributes to the adhesion of the corneal epithelium to Bowman's layer. To understand the adhesion complex better, an electron microscopic and immunofluorescence analysis was done of the reformation of the adhesion complex in small (1 mm) keratectomy wounds in the guinea pig cornea. In these wounds, the epithelium, hemidesmosomes, basal lamina, anchoring fibrils, and anterior stroma were removed. The wound bed was epithelialized completely by 24 hr after wounding. Immunofluorescence analyses involved the use of antibodies against plaque components of the hemidesmosome, an antibody against laminin, and an antibody against the collagen VII component of anchoring fibrils. At 18 hr after wounding, there was no morphologic evidence of hemidesmosomes at the epithelial-stromal interface. At 24 hr, hemidesmosomes were observed, with or without subjacent lamina densa. Furthermore, plaque components were detected by immunofluorescence in those cells in contact with the wound bed. In contrast, no type VII collagen was detected. On day 7, collagen VII, laminin, and bullous pemphigoid autoantibody markers colocalized along the wound bed as determined by immunofluorescence. However, at the ultrastructural level, even though the lamina densa of the basal lamina was observed primarily where hemidesmosomes were present, it remained incomplete. In this study, the precise temporal sequence in which components are incorporated into the assembling adhesion complex was described during wound healing. Furthermore, the possibility that the hemidesmosomal plaque nucleates the formation of the underlying basal lamina was discussed.

  8. Silicone-Based Adhesives with Highly Tunable Adhesion Force for Skin-Contact Applications.

    Science.gov (United States)

    Lee, Bong Kuk; Ryu, Jin Hwa; Baek, In-Bok; Kim, Yarkyeon; Jang, Won Ick; Kim, Sang-Hyeob; Yoon, Yong Sun; Kim, Seung Hwan; Hong, Seong-Gu; Byun, Sangwon; Yu, Han Young

    2017-11-01

    A fundamental approach to fabricating silicone-based adhesives with highly tunable adhesion force for the skin-contact applications is presented. Liquid blends consisting of vinyl-multifunctional polydimethylsiloxane (V-PDMS), hydride-terminated PDMS (H-PDMS), and a tackifier composed of a silanol-terminated PDMS/MQ resin mixture and the MQ resin are used as the adhesive materials. The peel adhesion force of addition-cured adhesives on the skin is increased by increasing the H-PDMS molecular weights and the tackifier content, and decreasing the H-PDMS/V-PDMS ratio. There is an inverse relationship between the adhesion force and the Young's modulus. The low-modulus adhesives with a low H-PDMS/V-PDMS ratio exhibit enhanced adhesion properties. The low-modulus adhesives with the high MQ resin content show significantly enhanced adhesion properties. These adhesives exhibit a wide range of modulus (2-499 kPa), and their adhesion force (0.04-5.38 N) is superior to commercially available soft silicone adhesives (0.82-2.79 N). The strong adhesives (>≈2 N) provide sufficient adhesion for fixing the flexible electrocardiogram (ECG) device to the skin in most daily activity. The human ECG signals are successfully recorded in real time. These results suggest that the silicone-based adhesives should be useful as an atraumatic adhesive for the skin-contact applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Highly Selective Activation of Heat Shock Protein 70 by Allosteric Regulation Provides an Insight into Efficient Neuroinflammation Inhibition

    Directory of Open Access Journals (Sweden)

    Li-Chao Wang

    2017-09-01

    Full Text Available Heat shock protein 70 (Hsp70 is widely involved in immune disorders, making it as an attractive drug target for inflammation diseases. Nonselective induction of Hsp70 upregulation for inflammation therapy could cause extensive interference in inflammation-unrelated protein functions, potentially resulting in side effects. Nevertheless, direct pharmacological activation of Hsp70 via targeting specific functional amino acid residue may provide an insight into precise Hsp70 function regulation and a more satisfactory treatment effect for inflammation, which has not been extensively focused. Here we show a cysteine residue (Cys306 for selective Hsp70 activation using natural small-molecule handelin. Covalent modification of Cys306 significantly elevates Hsp70 activity and shows more satisfactory anti-neuroinflammation effects. Mechanism study reveals Cys306 modification by handelin induces an allosteric regulation to facilitate adenosine triphosphate hydrolysis capacity of Hsp70, which leads to the effective blockage of subsequent inflammation signaling pathway. Collectively, our study offers some insights into direct pharmacological activation of Hsp70 by specially targeting functional cysteine residue, thus providing a powerful tool for accurately modulating neuroinflammation pathogenesis in human with fewer undesirable adverse effects.

  10. Neuroinflammation in the pathogenesis of Alzheimer´s disease. A rational framework for the search of novel therapeutic approaches

    Directory of Open Access Journals (Sweden)

    Ricardo Benjamin Maccioni

    2014-04-01

    Full Text Available Alzheimer disease (AD is the most common cause of dementia in people over 60 years old. The molecular and cellular alterations that trigger this disease are still diffuse, one of the reasons for the delay in finding an effective treatment. In the search for new targets to search for novel therapeutic avenues, clinical studies in patients who used anti-inflammatory drugs indicating a lower incidence of AD have been of value to support the neuroinflammatory hypothesis of the neurodegenerative processes and the role of innate immunity in this disease. Neuroinflammation appears to occur as a consequence of a series of damage signals, including trauma, infection, oxidative agents, redox iron, oligomers of tau and beta amyloid, etc. In this context, our theory of Neuroimmunomodulation focus on the link between neuronal damage and brain inflammatory process, mediated by the progressive activation of astrocytes and microglial cells with the consequent overproduction of proinflammatory agents. Here, we discuss about the role of microglial and astrocytic cells, the principal agents in neuroinflammation process, in the development of neurodegenerative diseases such as AD. In this context, we also evaluated the potential relevance of natural anti-inflammatory components, which include curcumin and the novel Andean Compound, as agents for AD prevention and as a coadjuvant for AD treatments.

  11. Chronic functional bowel syndrome enhances gut-brain axis dysfunction, neuroinflammation, cognitive impairment, and vulnerability to dementia.

    Science.gov (United States)

    Daulatzai, Mak Adam

    2014-04-01

    The irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disorder world wide that lasts for decades. The human gut harbors a diverse population of microbial organisms which is symbiotic and important for well being. However, studies on conventional, germ-free, and obese animals have shown that alteration in normal commensal gut microbiota and an increase in pathogenic microbiota-termed "dysbiosis", impact gut function, homeostasis, and health. Diarrhea, constipation, visceral hypersensitivity, and abdominal pain arise in IBS from the gut-induced dysfunctional metabolic, immune, and neuro-immune communication. Dysbiosis in IBS is associated with gut inflammation. Gut-related inflammation is pivotal in promoting endotoxemia, systemic inflammation, and neuroinflammation. A significant proportion of IBS patients chronically consume alcohol, non-steroidal anti-inflammatories, and fatty diet; they may also suffer from co-morbid respiratory, neuromuscular, psychological, sleep, and neurological disorders. The above pathophysiological substrate is underpinned by dysbiosis, and dysfunctional bidirectional "Gut-Brain Axis" pathways. Pathogenic gut microbiota-related systemic inflammation (due to increased lipopolysaccharide and pro-inflammatory cytokines, and barrier dysfunction), may trigger neuroinflammation enhancing dysfunctional brain regions including hippocampus and cerebellum. These as well as dysfunctional vago-vagal gut-brain axis may promote cognitive impairment. Indeed, inflammation is characteristic of a broad spectrum of neurodegenerative diseases that manifest demntia. It is argued that an awareness of pathophysiological impact of IBS and implementation of appropriate therapeutic measures may prevent cognitive impairment and minimize vulnerability to dementia.

  12. Inhibitory effect of ethanol extract of Nannochloropsis oceanica on lipopolysaccharide-induced neuroinflammation, oxidative stress, amyloidogenesis and memory impairment.

    Science.gov (United States)

    Choi, Ji Yeon; Hwang, Chul Ju; Lee, Hee Pom; Kim, Hee Sik; Han, Sang-Bae; Hong, Jin Tae

    2017-07-11

    Oxidative stress and neuroinflammation is implicated in the pathogenesis and development of Alzheimer's disease (AD). Here, we investigated the suppressive possibility of ethanol extract of Nannochloropsis oceanica (N. oceanica) on memory deficiency along with the fundamental mechanisms in lipopolysaccharide (LPS)-treated mice model. Among several extracts of 32 marine microalgae, ethanol extract of N. oceanica showed the most significant inhibitory effect on nitric oxide (NO) generation, NF-κB activity and β-secretase activity in cultured BV-2 cells, neuronal cells and Raw 264.7 cells. Ethanol extract of N. oceanica (50, 100 mg/kg) also ameliorated LPS (250 μg/kg)-induced memory impairment. We also found that ethanol extract of N. oceanica inhibited the LPS-induced expression of iNOS and COX-2. Furthermore, the production of reactive oxygen species (ROS), malondialdehyde (MDA) level as well as glutathione (GSH) level was also decreased by treatment of ethanol extract of N.oceanica. The ethanol extract of N. oceanica also suppresses IκB degradation as well as p50 and p65 translocation into the nucleus in LPS-treated mice brain. Associated with the inhibitory effect on neuroinflammation and oxidative stress, ethanol extract of N. oceanica suppressed Aβ1-42 generation through down-regulation of APP and BACE1 expression in in vivo. These results suggest that ethanol extract of N. oceanica ameliorated memory impairment via anti-inflammatory, anti-oxidant and anti-amyloidogenic mechanisms.

  13. Glucose-Dependent Insulinotropic Polypeptide Ameliorates Mild Traumatic Brain Injury-Induced Cognitive and Sensorimotor Deficits and Neuroinflammation in Rats.

    Science.gov (United States)

    Yu, Yu-Wen; Hsieh, Tsung-Hsun; Chen, Kai-Yun; Wu, John Chung-Che; Hoffer, Barry J; Greig, Nigel H; Li, Yazhou; Lai, Jing-Huei; Chang, Cheng-Fu; Lin, Jia-Wei; Chen, Yu-Hsin; Yang, Liang-Yo; Chiang, Yung-Hsiao

    2016-11-15

    Mild traumatic brain injury (mTBI) is a major public health issue, representing 75-90% of all cases of TBI. In clinical settings, mTBI, which is defined as a Glascow Coma Scale (GCS) score of 13-15, can lead to various physical, cognitive, emotional, and psychological-related symptoms. To date, there are no pharmaceutical-based therapies to manage the development of the pathological deficits associated with mTBI. In this study, the neurotrophic and neuroprotective properties of glucose-dependent insulinotropic polypeptide (GIP), an incretin similar to glucagon-like peptide-1 (GLP-1), was investigated after its steady-state subcutaneous administration, focusing on behavior after mTBI in an in vivo animal model. The mTBI rat model was generated by a mild controlled cortical impact (mCCI) and used to evaluate the therapeutic potential of GIP. We used the Morris water maze and novel object recognition tests, which are tasks for spatial and recognition memory, respectively, to identify the putative therapeutic effects of GIP on cognitive function. Further, beam walking and the adhesive removal tests were used to evaluate locomotor activity and somatosensory functions in rats with and without GIP administration after mCCI lesion. Lastly, we used immunohistochemical (IHC) staining and Western blot analyses to evaluate the inflammatory markers, glial fibrillary acidic protein (GFAP), amyloid-β precursor protein (APP), and bone marrow tyrosine kinase gene in chromosome X (BMX) in animals with mTBI. GIP was well tolerated and ameliorated mTBI-induced memory impairments, poor balance, and sensorimotor deficits after initiation in the post-injury period. In addition, GIP mitigated mTBI-induced neuroinflammatory changes on GFAP, APP, and BMX protein levels. These findings suggest GIP has significant benefits in managing mTBI-related symptoms and represents a novel strategy for mTBI treatment.

  14. Systemic administration of urocortin after intracerebral hemorrhage reduces neurological deficits and neuroinflammation in rats

    Directory of Open Access Journals (Sweden)

    Liew Hock-Kean

    2012-01-01

    Full Text Available Abstract Background Intracerebral hemorrhage (ICH remains a serious clinical problem lacking effective treatment. Urocortin (UCN, a novel anti-inflammatory neuropeptide, protects injured cardiomyocytes and dopaminergic neurons. Our preliminary studies indicate UCN alleviates ICH-induced brain injury when administered intracerebroventricularly (ICV. The present study examines the therapeutic effect of UCN on ICH-induced neurological deficits and neuroinflammation when administered by the more convenient intraperitoneal (i.p. route. Methods ICH was induced in male Sprague-Dawley rats by intrastriatal infusion of bacterial collagenase VII-S or autologous blood. UCN (2.5 or 25 μg/kg was administered i.p. at 60 minutes post-ICH. Penetration of i.p. administered fluorescently labeled UCN into the striatum was examined by fluorescence microscopy. Neurological deficits were evaluated by modified neurological severity score (mNSS. Brain edema was assessed using the dry/wet method. Blood-brain barrier (BBB disruption was assessed using the Evans blue assay. Hemorrhagic volume and lesion volume were assessed by Drabkin's method and morphometric assay, respectively. Pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6 expression was evaluated by enzyme-linked immunosorbent assay (ELISA. Microglial activation and neuronal loss were evaluated by immunohistochemistry. Results Administration of UCN reduced neurological deficits from 1 to 7 days post-ICH. Surprisingly, although a higher dose (25 μg/kg, i.p. also reduced the functional deficits associated with ICH, it is significantly less effective than the lower dose (2.5 μg/kg, i.p.. Beneficial results with the low dose of UCN included a reduction in neurological deficits from 1 to 7 days post-ICH, as well as a reduction in brain edema, BBB disruption, lesion volume, microglial activation and neuronal loss 3 days post-ICH, and suppression of TNF-α, IL-1β, and IL-6 production 1, 3 and 7 days post

  15. Alpha-chymotrypcin ameliorates neuroinflammation and apoptosis characterizing Alzheimer's disease-induced in ovarictomized rats.

    Science.gov (United States)

    El Dayem, Samiha M Abd; Ahmed, Hanaa H; Metwally, Fateheya; Foda, Fatma M Aly; Shalby, Aziza B; Zaazaa, Asmaa M A

    2013-07-01

    -chymotrypcin showed great improvement in the brain morphological structure with the disappearance of amyloid plaques. This study revealed that α-chymotrypcin significantly ameliorates the neuroinflammation characterizing Alzheimer's disease in ovariectomized rats due to it's proteolytic activity as well as it's anti-inflammatory effect. Copyright © 2012 Elsevier GmbH. All rights reserved.

  16. Parallelized TCSPC for Dynamic Intravital Fluorescence Lifetime Imaging: Quantifying Neuronal Dysfunction in Neuroinflammation

    Science.gov (United States)

    Radbruch, Helena; Andresen, Volker; Mossakowski, Agata; Siffrin, Volker; Seelemann, Thomas; Spiecker, Heinrich; Moll, Ingrid; Herz, Josephine; Hauser, Anja E.; Zipp, Frauke; Behne, Martin J.; Niesner, Raluca

    2013-01-01

    dysfunction in neuroinflammation. PMID:23613717

  17. Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

    Science.gov (United States)

    Tajuddin, Nuzhath; Moon, Kwan-Hoon; Marshall, S. Alex; Nixon, Kimberly; Neafsey, Edward J.; Kim, Hee-Yong; Collins, Michael A.

    2014-01-01

    Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼9 g/kg/d, achieving blood ethanol levels ∼375 mg/dl; “Majchrowicz” model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA (p-cPLA2), secretory PLA2 GIIA (sPLA2) and PARP-1 in regions incurring extensive neurodegeneration in this model—hippocampus, entorhinal cortex, and olfactory bulb—but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2) levels and increased brain “oxidative stress footprints” (4-hydroxynonenal-adducted proteins). For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼60 d) were ethanol-binged (100 mM or ∼450 mg/dl) for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013). Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3), known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins). Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models

  18. Neuroprotective effect of nerolidol against neuroinflammation and oxidative stress induced by rotenone.

    Science.gov (United States)

    Javed, Hayate; Azimullah, Sheikh; Abul Khair, Salema B; Ojha, Shreesh; Haque, M Emdadul

    2016-08-22

    Parkinson disease (PD) is a movement disorder affecting 1 % of people over the age of 60. The etiology of the disease is unknown; however, accumulating evidence suggests that mitochondrial defects, oxidative stress, and neuroinflammation play important roles in developing the disease. Current medications for PD can only improve its symptoms, but are unable to halt its progressive nature. Although many therapeutic approaches are available, new drugs are urgently needed for the treatment of PD. Thus, the present study was undertaken to investigate the neuroprotective potential of nerolidol, a sesquiterpene alcohol, on a rotenone-induced experimental model of PD, where male Wistar rats intraperitoneally received rotenone (ROT) at a dose of 2.5 mg/kg of body weight once daily for 4 weeks. Nerolidol, which has antioxidant and anti-inflammatory properties, was injected intraperitoneally at 50 mg/kg of body weight, once daily for 4 weeks, and at 30 min prior to ROT administration. ROT administration significantly reduced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of the antioxidant tripeptide glutathione (GSH). Moreover, ROT increased the levels of the lipid peroxidation product malondialdehyde (MDA), proinflammatory cytokines (IL-1β, IL-6, and TNF-α), and inflammatory mediators (COX-2 and iNOS) in rat brain tissues. Immunostaining of brain tissue sections revealed a significant increase in the number of activated astrocytes (GFAP) and microglia (Iba-1), along with the concomitant loss of dopamine (DA) neurons in the substantia nigra pars compacta and dopaminergic nerve fibers in the striatum of ROT-treated rats. As expected, nerolidol supplementation to ROT-injected rats significantly increased the level of SOD, CAT, and GSH, and decreased the level of MDA. Nerolidol also inhibited the release of proinflammatory cytokines and inflammatory mediators. Finally, nerolidol treatment prevented ROT-induced glial

  19. Parallelized TCSPC for dynamic intravital fluorescence lifetime imaging: quantifying neuronal dysfunction in neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Jan Leo Rinnenthal

    neuronal dysfunction in neuroinflammation.

  20. Neuroinflammation and neurodegeneration in adult rat brain from binge ethanol exposure: abrogation by docosahexaenoic acid.

    Directory of Open Access Journals (Sweden)

    Nuzhath Tajuddin

    Full Text Available Evidence that brain edema and aquaporin-4 (AQP4 water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2 family members and poly (ADP-ribose polymerase-1 (PARP-1. In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼ 9 g/kg/d, achieving blood ethanol levels ∼ 375 mg/dl; "Majchrowicz" model significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2, phospho-cPLA2 GIVA (p-cPLA2, secretory PLA2 GIIA (sPLA2 and PARP-1 in regions incurring extensive neurodegeneration in this model--hippocampus, entorhinal cortex, and olfactory bulb--but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2 levels and increased brain "oxidative stress footprints" (4-hydroxynonenal-adducted proteins. For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼ 60 d were ethanol-binged (100 mM or ∼ 450 mg/dl for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013. Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3, known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins. Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models

  1. Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice.

    Science.gov (United States)

    Soong, Lynn; Shelite, Thomas R; Xing, Yan; Kodakandla, Harica; Liang, Yuejin; Trent, Brandon J; Horton, Paulina; Smith, Kathryn C; Zhao, Zhenyang; Sun, Jiaren; Bouyer, Donald H; Cai, Jiyang

    2017-07-01

    Scrub typhus is a life-threatening disease, due to infection with O. tsutsugamushi, a Gram-negative bacterium that preferentially replicates in endothelial cells and professional phagocytes. Meningoencephalitis has been reported in scrub typhus patients and experimentally-infected animals; however, the neurological manifestation and its underlying mechanisms remain poorly understood. To address this issue, we focused on Orientia tsutsugamushi Karp strain (OtK), and examined host responses in the brain during lethal versus self-healing scrub typhus disease in our newly established murine models. Following inoculation with a lethal dose of OtK, mice had a significant increase in brain transcripts related to pathogen-pattern recognition receptors (TLR2, TLR4, TLR9), type-1 responses (IFN-γ, TNF-α, CXCL9, CXCR3), and endothelial stress/damage such as angiopoietins, but a rapid down-regulation of Tie2. Sublethal infection displayed similar trends, implying the development of type 1-skewed proinflammatory responses in infected brains, independent of time and disease outcomes. Focal hemorrhagic lesions and meningitis were evident in both infection groups, but pathological changes were more diffuse and frequent in lethal infection. At 6-10 days of lethal infection, the cortex and cerebellum sections had increased ICAM-1-positive staining in vascular cells, as well as increased detection of CD45+ leukocytes, CD3+ T cells, IBA1+ phagocytes, and GFAP+ astrocytes, but a marked loss of occludin-positive tight junction staining, implying progressive endothelial activation/damage and cellular recruitment in inflamed brains. Orientia were sparse in the brains, but readily detectable within lectin+ vascular and IBA-1+ phagocytic cells. These CNS alterations were consistent with type 1-skewed, IL-13-suppressed responses in lethally-infected mouse lungs. This is the first report of type 1-skewed neuroinflammation and cellular activation, accompanied with vascular activation

  2. Activated Microglia Targeting Dendrimer-Minocycline Conjugate as Therapeutics for Neuroinflammation.

    Science.gov (United States)

    Sharma, Rishi; Kim, Soo-Young; Sharma, Anjali; Zhang, Zhi; Kambhampati, Siva Pramodh; Kannan, Sujatha; Kannan, Rangaramanujam M

    2017-11-15

    day 1 to rabbit kits with a clinically relevant phenotype of cerebral palsy. The in vivo imaging study indicates that Cy5-D-mino crossed the impaired blood-brain barrier and co-localized with activated microglia at the periventricular white matter areas, including the corpus callosum and the angle of the lateral ventricle, with significant implications for positive therapeutic outcomes. The enhanced efficacy of D-mino, when combined with the inherent neuroinflammation-targeting capability of the PAMAM dendrimers, may provide new opportunities for targeted drug delivery to treat neurological disorders.

  3. Reproductive outcome following treatment of intrauterine adhesions ...

    African Journals Online (AJOL)

    Conclusion: The reproductive outcome following treatment of intrauterine adhesions in this centre is not encouraging and needs improvement. Adoption of more successful treatment modalities like hysteroscopic adhesiolysis is advocated. . Keywords: Reproductive outcome; Intrauterine adhesions; Abuja Nigerian Journal of ...

  4. Adhesion of Antireflective Coatings in Multijunction Photovoltaics

    Energy Technology Data Exchange (ETDEWEB)

    Brock, Ryan; Miller, David C.; Dauskardt, Reinhold H.

    2016-11-21

    The development of a new composite dual cantilever beam (cDCB) thin-film adhesion testing method is reported, which allows the measurement of adhesion on the fragile thin substrates used in multijunction photovoltaics. We address the adhesion of several antireflective coating systems on multijunction cells. By varying interface chemistry and morphology, we demonstrate the ensuing effects on adhesion and help to develop an understanding of how high adhesion can be achieved, as adhesion values ranging from 0.5 J/m2 to 10 J/m2 were measured. Damp Heat (85 degrees C/85% RH) was used to invoke degradation of interfacial adhesion. We show that even with germanium substrates that fracture easily, quantitative measurements of adhesion can still be made at high test yield. The cDCB test is discussed as an important new methodology, which can be broadly applied to any system that makes use of thin, brittle, or otherwise fragile substrates.

  5. Adhesion of biocompatible and biodegradable micropatterned surfaces

    NARCIS (Netherlands)

    Kaiser, J.S.; Kamperman, M.M.G.; Souza, E.J.; Schick, B.; Arzt, E.

    2011-01-01

    We studied the effects of pillar dimensions and stiffness of biocompatible and biodegradable micropatterned surfaces on adhesion on different compliant substrates. The micropatterned adhesives were based on biocompatible polydimethylsiloxane (PDMS) and biodegradable poly(lactic-co-glycolic) acid

  6. Syndecan proteoglycans and cell adhesion

    DEFF Research Database (Denmark)

    Woods, A; Oh, E S; Couchman, J R

    1998-01-01

    It is now becoming clear that a family of transmembrane proteoglycans, the syndecans, have important roles in cell adhesion. They participate through binding of matrix ligand to their glycosaminoglycan chains, clustering, and the induction of signaling cascades to modify the internal microfilament...

  7. Bio-Inspired Controllable Adhesive

    Science.gov (United States)

    2008-12-01

    well as many species of insect, have evolved a robust reversible adhesion mechanism, enabling them to traverse rough, smooth, vertical or inverted...such as enabling microrobotics to explore extraterrestrial surfaces or harsh climates otherwise not accessible to man. Current work is also

  8. Lignin-Furfural Based Adhesives

    National Research Council Canada - National Science Library

    Dongre, Prajakta; Driscoll, Mark; Amidon, Thomas; Bujanovic, Biljana

    2015-01-01

    ... (SEC). The effect of pH (0.3, 0.65 and 1), ex situ furfural, and curing conditions on the tensile properties of adhesive reinforced glass fibers is determined and compared to the reinforcement level of commercially available PF resin...

  9. intrauterine adhesions in abuja, nigeria.

    African Journals Online (AJOL)

    pain or with recurrent abortions 3, and therefore an important cause of ... therapeutic endoscopy at National Hospital, Abuja,. Nigeria, this paper .... pain. Recurrent 2 2 (100) - - - l (50) abortion. Normal 1 1 (100) - - - - menses. 166 Nigerian Jaurnal of Clinical Practice. Dec. 2006, Vol. 9(2). Intrauterine adhesions. E.R. Efetie.

  10. Intestinal Obstruction from an Adhesion

    African Journals Online (AJOL)

    Intestinal Obstruction from an Adhesion. Bahd Mimicking Peritonitis due to a _. Complicated Induced Unsafe Abortion: A Case Report. ABSTRACT. Miss EN. a 19—year old nullipara presented at the Accidents and Emergency unit of the Ebonyi State University. Teaching Hospital (EBSUTH), Abakaliki on the 17/5/06 with ...

  11. Ovalbumin as a Wood Adhesive

    Science.gov (United States)

    Charles R. Frihart; Holly Satori; Zhu Rongxian; Michael J. Birkeland

    2014-01-01

    Use of proteins to bond wood dominated industrial production until the middle of the 20th century (1). The ensuing creation of the plywood and glulam beam industries allowed for more efficient use of wood resources than is possible with solid wood products. Many protein sources have been used as adhesives, including plant (soybean) and animal (blood, fish scales,...

  12. Candida biofilms: is adhesion sexy?

    Science.gov (United States)

    Soll, David R

    2008-08-26

    The development of Candida albicans biofilms requires two types of adhesion molecule - the Als proteins and Hwp1. Mutational analyses have recently revealed that these molecules play complementary roles, and their characteristics suggest that they may have evolved from primitive mating agglutinins.

  13. Inflammatory pathology markers (activated microglia and reactive astrocytes) in early and late onset Alzheimer disease: a post mortem study.

    Science.gov (United States)

    Taipa, R; Ferreira, V; Brochado, P; Robinson, A; Reis, I; Marques, F; Mann, D M; Melo-Pires, M; Sousa, N

    2017-10-17

    The association between the pathological features of AD and dementia is stronger in younger old persons than in older old persons suggesting that additional factors are involved in the clinical expression of dementia in the oldest old. Cumulative data suggests that neuroinflammation plays a prominent role in Alzheimer's disease (AD) and different studies reported an age-associated dysregulation of the neuroimmune system. Consequently, we sought to characterize the pattern of microglial cell activation and astrogliosis in brain post mortem tissue of pathologically confirmed cases of early and late onset AD (EOAD and LOAD) and determine their relation to age. Immunohistochemistry (CD68 and glial fibrillary acidic protein) with morphometric analysis of astroglial profiles in 36 cases of AD and 28 similarly aged controls. Both EOAD and LOAD groups had higher microglial scores in CA1, entorhinal and temporal cortices, and higher astroglial response in CA1, dentate gyrus, entorhinal and temporal cortices, compared to aged matched controls. Additionally, EOAD had higher microglial scores in subiculum, entorhinal and temporal subcortical white matter, and LOAD higher astrogliosis in CA2 region. Overall, we found that the neuroinflammatory pathological markers in late stage AD human tissue to have a similar pattern in both EOAD and LOAD, though the severity of the pathological markers in the younger group was higher. Understanding the age effect in AD will be important when testing modifying agents that act on the neuroinflammation. © 2017 British Neuropathological Society.

  14. Peritoneal adhesions after laparoscopic gastrointestinal surgery

    OpenAIRE

    Mais, Valerio

    2014-01-01

    Although laparoscopy has the potential to reduce peritoneal trauma and post-operative peritoneal adhesion formation, only one randomized controlled trial and a few comparative retrospective clinical studies have addressed this issue. Laparoscopy reduces de novo adhesion formation but has no efficacy in reducing adhesion reformation after adhesiolysis. Moreover, several studies have suggested that the reduction of de novo post-operative adhesions does not seem to have a significant clinical im...

  15. T cell activation markers “CD45RO and CD45RA”; neutrophil CD11b ...

    African Journals Online (AJOL)

    Ehab

    activation markers CD45RA/CD45RO and neutrophil CD11b by flow cytometry and soluble tumor necrosis factor ... CD45RO, CD45RO), neutrophil activation marker (CD11b) and soluble TNF receptor 1 are useful early indicators of ..... sepsis with cytokines adhesion molecule, and C-reactive protein in preterm very low.

  16. Transverse Reinforcement of Adhesive Joints

    Science.gov (United States)

    Sapozhnikov, S.; Shakirov, A.

    2015-05-01

    The shear of single-lap adhesive joints causes significant peel stresses in the adhesive layer, which is a particularly urgent problem for low-modulus polyurethane compositions. An experimental and computational analysis of various methods for increasing the load-bearing capacity of the joints by their strengthening with metallic z-elements was carried out. This strengthening hinders their delamination by the action of peel stresses, which allows one to reduce the overall dimensions and weight of adhesive joints. Two main strengthening methods were considered: with steel tapping screws (of diameter 2.5 mm) and blind aluminum rivets (of diameter 4.0 mm). The peculiarity of the strengthening lies in the fact that z-elements of minimum available diameter were used for reducing the effect of stress concentrations on the strength of the joints. The test of specimens for each type of strengthening showed an average increase in the ultimate load by 40% for the threaded reinforcements and by 10% for the rivets. During an analysis of stress state of the joints by the FEM, the nonlinear behavior of constituent materials and stress concentration in the region of reinforcing elements were taken into account. The mechanical properties of the adhesive layer and the GFRP covering were determined in separate experiments. The analysis showed that the weight of the reinforced adhesive joints could be lowered by 20-25% relative to that of unreinforced ones without reducing their load-bearing capacity. An additional effect caused by using the threaded reinforcing elements was a more than threefold increase in their rigidity as compared with that of analogous nonreinforced ones.

  17. Aspirin augments hyaluronidase induced adhesion inhibition ...

    African Journals Online (AJOL)

    Postoperative adhesions occur after virtually all abdomino-pelvic surgery and are the leading cause of intestinal obstruction and other gynaecologic problems. We used an animal model to test the efficacy of combined administration of aspirin and hyaluronidase on adhesion formation. Adhesions were induced using ...

  18. Current dental adhesives systems. A narrative review.

    Science.gov (United States)

    Milia, Egle; Cumbo, Enzo; Cardoso, Rielson Jose A; Gallina, Giuseppe

    2012-01-01

    Adhesive dentistry is based on the development of materials which establish an effective bond with the tooth tissues. In this context, adhesive systems have attracted considerable research interest in recent years. Successful adhesive bonding depends on the chemistry of the adhesive, on appropriate clinical handling of the material as well as on the knowledge of the morphological changes caused on dental tissue by different bonding procedures. This paper outlines the status of contemporary adhesive systems, with particular emphasis on chemical characteristics and mode of interaction of the adhesives with enamel and dentinal tissues. Dental adhesives are used for several clinical applications and they can be classified based on the clinical regimen in "etch-and-rinse adhesives" and "self-etch adhesives". Other important considerations concern the different anatomical characteristics of enamel and dentine which are involved in the bonding procedures that have also implications for the technique used as well as for the quality of the bond. Etch-and-rinse adhesive systems generally perform better on enamel than self-etching systems which may be more suitable for bonding to dentine. In order to avoid a possible loss of the restoration, secondary caries or pulp damage due to bacteria penetration or due to cytotoxicity effects of eluted adhesive components, careful consideration of several factors is essential in selecting the suitable bonding procedure and adhesive system for the individual patient situation.

  19. Influence of substrate modulus on gecko adhesion

    Science.gov (United States)

    Klittich, Mena R.; Wilson, Michael C.; Bernard, Craig; Rodrigo, Rochelle M.; Keith, Austin J.; Niewiarowski, Peter H.; Dhinojwala, Ali

    2017-01-01

    The gecko adhesion system fascinates biologists and materials scientists alike for its strong, reversible, glue-free, dry adhesion. Understanding the adhesion system’s performance on various surfaces can give clues as to gecko behaviour, as well as towards designing synthetic adhesive mimics. Geckos encounter a variety of surfaces in their natural habitats; tropical geckos, such as Gekko gecko, encounter hard, rough tree trunks as well as soft, flexible leaves. While gecko adhesion on hard surfaces has been extensively studied, little work has been done on soft surfaces. Here, we investigate for the first time the influence of macroscale and nanoscale substrate modulus on whole animal adhesion on two different substrates (cellulose acetate and polydimethylsiloxane) in air and find that across 5 orders of magnitude in macroscale modulus, there is no change in adhesion. On the nanoscale, however, gecko adhesion is shown to depend on substrate modulus. This suggests that low surface-layer modulus may inhibit the gecko adhesion system, independent of other influencing factors such as macroscale composite modulus and surface energy. Understanding the limits of gecko adhesion is vital for clarifying adhesive mechanisms and in the design of synthetic adhesives for soft substrates (including for biomedical applications and wearable electronics). PMID:28287647

  20. Nonwoven glass fiber mat reinforces polyurethane adhesive

    Science.gov (United States)

    Roseland, L. M.

    1967-01-01

    Nonwoven glass fiber mat reinforces the adhesive properties of a polyurethane adhesive that fastens hardware to exterior surfaces of aluminum tanks. The mat is embedded in the uncured adhesive. It ensures good control of the bond line and increases the peel strength.

  1. Influence of substrate modulus on gecko adhesion

    Science.gov (United States)

    Klittich, Mena R.; Wilson, Michael C.; Bernard, Craig; Rodrigo, Rochelle M.; Keith, Austin J.; Niewiarowski, Peter H.; Dhinojwala, Ali

    2017-03-01

    The gecko adhesion system fascinates biologists and materials scientists alike for its strong, reversible, glue-free, dry adhesion. Understanding the adhesion system’s performance on various surfaces can give clues as to gecko behaviour, as well as towards designing synthetic adhesive mimics. Geckos encounter a variety of surfaces in their natural habitats; tropical geckos, such as Gekko gecko, encounter hard, rough tree trunks as well as soft, flexible leaves. While gecko adhesion on hard surfaces has been extensively studied, little work has been done on soft surfaces. Here, we investigate for the first time the influence of macroscale and nanoscale substrate modulus on whole animal adhesion on two different substrates (cellulose acetate and polydimethylsiloxane) in air and find that across 5 orders of magnitude in macroscale modulus, there is no change in adhesion. On the nanoscale, however, gecko adhesion is shown to depend on substrate modulus. This suggests that low surface-layer modulus may inhibit the gecko adhesion system, independent of other influencing factors such as macroscale composite modulus and surface energy. Understanding the limits of gecko adhesion is vital for clarifying adhesive mechanisms and in the design of synthetic adhesives for soft substrates (including for biomedical applications and wearable electronics).

  2. 21 CFR 878.4380 - Drape adhesive.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Drape adhesive. 878.4380 Section 878.4380 Food and... GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4380 Drape adhesive. (a) Identification. A drape adhesive is a device intended to be placed on the skin to attach a surgical drape. (b...

  3. Neuroinflammation in the pathophysiology of Parkinson's disease : Evidence from animal models to human in vivo studies with [C-11]-PKI1195 PET

    NARCIS (Netherlands)

    Bartels, Anna L.; Leenders, Klaus L.

    2007-01-01

    Increasing evidence suggests that neuroinflammation is an active process in Parkinson's disease (PD) that contributes to ongoing neurodegeneration. PD brains and experimental PD models show elevated cytokine levels and upregulation of inflammatory-associated factors as cyclo-oxygenase-2 and

  4. Initial Homotypic Cell Pair Adhesion in Regenerating Hydra Facilitates Subsequent Adhesion of Homotypic Cells

    Science.gov (United States)

    Takaku, Y.; Hariyama, T.; Tsukahara, Y.

    In Hydra vulgaris at the level of dissociated single cells endodermal cells adhere to each other more readily than to ectodermal cells at the initial adhesion. The time required for adhesion to occur between two adjacent cells is shorter for both endodermal and ectodermal homotypic cell adhesions once the initial adhesion of the first pair of cells has been established. It is confirmed that contact of an aggregated pair with additional homotypic cells facilitates the occurrence of homotypic adhesions; heterotypic adhesions are discouraged. This suggests that adhesion of homotypic cells contributes to an increased readiness for subsequent homotypic cells to adhere.

  5. Expression of metallothionein-I, -II, and -III in Alzheimer disease and animal models of neuroinflammation

    DEFF Research Database (Denmark)

    Hidalgo, Juan; Penkowa, Milena; Espejo, Carmen

    2006-01-01

    . In Alzheimer disease (AD), a major neurodegenerative disease, clear signs of inflammation and oxidative stress were detected associated with amyloid plaques. Furthermore, the number of cells expressing apoptotic markers was also significantly increased in these plaques. As expected, MT-I and MT...

  6. Longitudinal investigation of neuroinflammation and metabolite profiles in the APPswe ×PS1Δe9 transgenic mouse model of Alzheimer's disease.

    Science.gov (United States)

    Chaney, Aisling; Bauer, Martin; Bochicchio, Daniela; Smigova, Alison; Kassiou, Michael; Davies, Karen E; Williams, Steve R; Boutin, Herve

    2018-02-01

    There is increasing evidence linking neuroinflammation to many neurological disorders including Alzheimer's disease (AD); however, its exact contribution to disease manifestation and/or progression is poorly understood. Therefore, there is a need to investigate neuroinflammation in both health and disease. Here, we investigate cognitive decline, neuroinflammatory and other pathophysiological changes in the APPswe ×PS1Δe9 transgenic mouse model of AD. Transgenic (TG) mice were compared to C57BL/6 wild type (WT) mice at 6, 12 and 18 months of age. Neuroinflammation was investigated by [18 F]DPA-714 positron emission tomography and myo-inositol levels using 1 H magnetic resonance spectroscopy (MRS) in vivo. Neuronal and cellular dysfunction was investigated by looking at N-acetylaspartate (NAA), choline-containing compounds, taurine and glutamate also using MRS. Cognitive decline was first observed at 12 m of age in the TG mice as assessed by working memory tests . A significant increase in [18 F]DPA-714 uptake was seen in the hippocampus and cortex of 18 m-old TG mice when compared to age-matched WT mice and 6 m-old TG mice. No overall effect of gene was seen on metabolite levels; however, a significant reduction in NAA was observed in 18 m-old TG mice when compared to WT. In addition, age resulted in a decrease in glutamate and an increase in choline levels. Therefore, we can conclude that increased neuroinflammation and cognitive decline are observed in TG animals, whereas NAA alterations occurring with age are exacerbated in the TG mice. These results support the role of neuroinflammation and metabolite alteration in AD and in ageing. © 2017 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

  7. Adhesives for fixed orthodontic bands.

    Science.gov (United States)

    Millett, Declan T; Glenny, Anne-Marie; Mattick, Rye Cr; Hickman, Joy; Mandall, Nicky A

    2016-10-25

    Orthodontic treatment involves using fixed or removable appliances (dental braces) to correct the positions of teeth. It has been shown that the quality of treatment result obtained with fixed appliances is much better than with removable appliances. Fixed appliances are, therefore, favoured by most orthodontists for treatment. The success of a fixed orthodontic appliance depends on the metal attachments (brackets and bands) being attached securely to the teeth so that they do not become loose during treatment. Brackets are usually attached to the front and side teeth, whereas bands (metal rings that go round the teeth) are more commonly used on the back teeth (molars). A number of adhesives are available to attach bands to teeth and it is important to understand which group of adhesives bond most reliably, as well as reducing or preventing dental decay during the treatment period. To evaluate the effectiveness of the adhesives used to attach bands to teeth during fixed appliance treatment, in terms of:(1) how often the bands come off during treatment; and(2) whether they protect the banded teeth against decay during fixed appliance treatment. The following electronic databases were searched: Cochrane Oral Health's Trials Register (searched 2 June 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 5) in the Cochrane Library (searched 2 June 2016), MEDLINE Ovid (1946 to 2 June 2016) and EMBASE Ovid (1980 to 2 June 2016). We searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. Randomised and controlled clinical trials (RCTs and CCTs) (including split-mouth studies) of adhesives used to attach orthodontic bands to molar teeth were selected. Patients with full arch fixed orthodontic appliance(s) who had bands attached to molars were included. All review authors

  8. Adhesive Behavior of Single Carbon Nanotubes

    Science.gov (United States)

    Maeno, Yohei; Ishikawa, Atsunori; Nakayama, Yoshikazu

    2010-06-01

    We examined the adhesion of a carbon nanotube (CNT) tip using a manipulation technique with a transmission electron microscope. In addition, we estimated the maximum normal adhesion possibility of a CNT-based gecko tape. The adhesive behavior of a single isolated CNT to Au solid surfaces has high normal strength (6.84 nN), which has a linear relation to the cross section of a CNT, indicating the mechanism: van der Waals force was inferred from the contact of two flat surfaces. Adhesion measurements conducted on several surface materials verify that the surface chemistry affects adhesive properties of CNT tips.

  9. A review of high-temperature adhesives

    Science.gov (United States)

    St.clair, A. K.; St.clair, T. L.

    1981-01-01

    The development of high temperature adhesives and polyphenylquinoxalines (PPQ) is reported. Thermoplastic polyimides and linear PPQ adhesive are shown to have potential for bonding both metals and composite structures. A nadic terminated addition polyimide adhesive, LARC-13, and an acetylene terminated phenylquinoxaline (ATPQ) were developed. Both of the addition type adhesives are shown to be more readily processable than linear materials but less thermooxidatively stable and more brittle. It is found that the addition type adhesives are able to perform, at elevated temperatures up to 595 C where linear systems fail thermoplastically.

  10. Gecko adhesion pad: a smart surface?

    Science.gov (United States)

    Pesika, Noshir S.; Zeng, Hongbo; Kristiansen, Kai; Zhao, Boxin; Tian, Yu; Autumn, Kellar; Israelachvili, Jacob

    2009-11-01

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  11. Gecko adhesion pad: a smart surface?

    Energy Technology Data Exchange (ETDEWEB)

    Pesika, Noshir S [Chemical and Biomolecular Engineering Department, Tulane University, New Orleans, LA 70118 (United States); Zeng Hongbo [Chemical and Materials Engineering Department, University of Alberta, Edmonton, AB, T6G 2V4 (Canada); Kristiansen, Kai; Israelachvili, Jacob [Chemical Engineering Department, University of California, Santa Barbara, CA 93117 (United States); Zhao, Boxin [Chemical Engineering Department and Waterloo Institute of Nanotechnology, University of Waterloo, Ontario, N2L 3G1 (Canada); Tian Yu [State Key Laboratory of Tribology, Department of Precision Instruments, Tsinghua University, Beijing 100084 (China); Autumn, Kellar, E-mail: npesika@tulane.ed [Department of Biology, Lewis and Clark College, Portland, OR 97219 (United States)

    2009-11-18

    Recently, it has been shown that humidity can increase the adhesion of the spatula pads that form the outermost (adhesive) surface of the tokay gecko feet by 50% relative to the main adhesion mechanism (i.e. van der Waals adhesive forces), although the mechanism by which the enhancement is realized is still not well understood. A change in the surface hydrophobicity of a gecko setal array is observed when the array, which supports the spatulae, is exposed to a water drop for more than 20 min, suggesting a change in the hydrophilic-lyophilic balance (HLB), and therefore of the conformation of the surface proteins. A surface force apparatus (SFA) was used to quantify these changes, i.e. in the adhesion and friction forces, while shearing the setal array against a silica surface under (i) dry conditions, (ii) 100% humidity and (iii) when fully immersed in water. The adhesion increased in the humid environment but greatly diminished in water. Although the adhesion forces changed significantly, the friction forces remained unaffected, indicating that the friction between these highly textured surfaces is 'load-controlled' rather than 'adhesion-controlled'. These results demonstrate that the gecko adhesive pads have the ability to exploit environmental conditions to maximize their adhesion and stabilize their friction forces. Future designs of synthetic dry adhesives inspired by the gecko can potentially include similar 'smart' surfaces that adapt to their environment.

  12. Conformal adhesion enhancement on biomimetic microstructured surfaces.

    Science.gov (United States)

    Shahsavan, Hamed; Zhao, Boxin

    2011-06-21

    Inspired by the superior adhesive ability of the gecko foot pad, we report an experimental study of conformal adhesion of a soft elastomer thin film on biomimetic micropatterned surfaces (micropillars), showing a remarkable adhesion enhancement due to the surface patterning. The adhesion of a low-surface-energy poly(dimethylsiloxane) tape to a SU-8 micropatterned surface was found be able to increase by 550-fold as the aspect ratio increases from 0 to 6. The dependency of the adhesion enhancement on the aspect ratio is highly nonlinear. A series of peeling experiment coupled with optical interference imaging were performed to investigate the adhesion enhancement as a function of the height of the micropillars and the associated delamination mechanisms. Local elastic energy dissipation, side-wall friction, and plastic deformations were analyzed and discussed in terms of their contributions to the adhesion enhancement. We conclude that the local adhesion and friction events of pulling micropillars out of the embedded polymer film play a primary role in the observed adhesion enhancement. The technical implications of this local friction-based adhesion enhancement mechanism were discussed for the effective assembly of similar or dissimilar material components at small scales. The combined use of the micro/nanostructured surfaces with the van der Waals interactions seem to be a potentially more universal solution than the conventional adhesive bonding technology, which depends on the chemical and viscoelastic properties of the materials. © 2011 American Chemical Society

  13. Adhesion of liquid droplets to rough surfaces.

    Science.gov (United States)

    Li, Ri; Alizadeh, Azar; Shang, Wen

    2010-10-01

    We study the adhesion of liquid droplets to rough surfaces, focusing on how adhesion changes with surface chemistry and roughness. For hydrophobic surfaces (equilibrium contact angle θ(e)>90°), although increasing surface roughness augments apparent contact angle, it does not necessarily always reduce adhesion. In a domain defined by roughness and equilibrium contact angle, this study identifies regions where adhesion increases or decreases with increasing roughness. The two regions do not border at θ(e)=90°. It is found that making surfaces with low roughness ratio (close to 1) does not reduce adhesion unless the surface material is highly hydrophobic (θ(e)>120°). In other words, to reduce adhesion for existing hydrophobic materials (90°adhesion, the geometry of microstructures should be designed such that wetted fraction decreases with increasing roughness ratio. This study is of particular importance for the design of textured superhydrophobic surfaces.

  14. Cell adhesion molecules and sleep.

    Science.gov (United States)

    O'Callaghan, Emma Kate; Ballester Roig, Maria Neus; Mongrain, Valérie

    2017-03-01

    Cell adhesion molecules (CAMs) play essential roles in the central nervous system, where some families are involved in synaptic development and function. These synaptic adhesion molecules (SAMs) are involved in the regulation of synaptic plasticity, and the formation of neuronal networks. Recent findings from studies examining the consequences of sleep loss suggest that these molecules are candidates to act in sleep regulation. This review highlights the experimental data that lead to the identification of SAMs as potential sleep regulators, and discusses results supporting that specific SAMs are involved in different aspects of sleep regulation. Further, some potential mechanisms by which SAMs may act to regulate sleep are outlined, and the proposition that these molecules may serve as molecular machinery in the two sleep regulatory processes, the circadian and homeostatic components, is presented. Together, the data argue that SAMs regulate the neuronal plasticity that underlies sleep and wakefulness. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  15. Platelet inhibition and endothelial cell adhesion on elastin-like polypeptide surface modified materials.

    Science.gov (United States)

    Blit, Patrick H; McClung, W Glenn; Brash, John L; Woodhouse, Kimberly A; Santerre, J Paul

    2011-09-01

    Platelet adhesion and activation are important early markers of biomaterial blood compatibility, while surfaces that promote enhanced endothelial cell adhesion and eNOS expression are strategic targets for long term vascular graft applications. Materials surface modified with fluorinated surface modifiers, containing peptides inspired from elastin cross-linking domains, have been used for the cross-linking of elastin-like polypeptide 4 (ELP4) macromolecules onto polyurethane surfaces. In the present study, ELP4 modified polyurethanes were evaluated in vitro to assess platelet adhesion, microparticle formation and bulk platelet activation following blood-material interactions. Reduced platelet adhesion and bulk platelet activation were observed following contact between reconstituted human blood and the ELP4 materials, relative to the uncoated base polyurethane controls. ELP4 modified materials also promoted endothelial cell adhesion and retention over a period of one week and showed that the endothelial cells exhibited an organized actin cytoskeleton and enhanced endothelial nitric oxide synthase (eNOS) expression relative to the control surfaces. These results indicate that polyurethane elastomers modified with ELP4 covalently bound to fluorinated surface modifiers provide a promising approach for endowing synthetic elastomers with both reduced blood platelet activation properties and enhanced endothelial cell adhesion for potential use in vascular graft applications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Sickle cell disease biochip: a functional red blood cell adhesion assay for monitoring sickle cell disease

    Science.gov (United States)

    ALAPAN, YUNUS; KIM, CEONNE; ADHIKARI, ANIMA; GRAY, KAYLA E.; GURKAN-CAVUSOGLU, EVREN; LITTLE, JANE A.; GURKAN, UMUT A.

    2016-01-01

    Sickle cell disease (SCD) afflicts millions of people worldwide and is associated with considerable morbidity and mortality. Chronic and acute vaso-occlusion are the clinical hallmarks of SCD and can result in pain crisis, widespread organ damage, and early movtality. Even though the molecular underpinnings of SCD were identified more than 60 years ago, there are no molecular or biophysical markers of disease severity that are feasibly measured in the clinic. Abnormal cellular adhesion to vascular endothelium is at the root of vaso-occlusion. However, cellular adhesion is not currently evaluated clinically. Here, we present a clinically applicable microfluidic device (SCD biochip) that allows serial quantitative evaluation of red blood cell (RBC) adhesion to endothelium-associated protein-immobilized microchannels, in a closed and preprocessing-free system. With the SCD biochip, we have analyzed blood samples from more than 100 subjects and have shown associations between the measured RBC adhesion to endothelium-associated proteins (fibronectin and laminin) and individual RBC characteristics, including hemoglobin content, fetal hemoglobin concentration, plasma lactate dehydrogenase level, and reticulocyte count. The SCD biochip is a functional adhesion assay, reflecting quantitative evaluation of RBC adhesion, which could be used at baseline, during crises, relative to various long-term complications, and before and after therapeutic interventions. PMID:27063958

  17. Fracture toughness of two dentin adhesives.

    Science.gov (United States)

    Howard, Kimberly; Söderholm, Karl-Johan M

    2010-12-01

    Test the hypothesis that a self-etching adhesive is more likely to fail at the dentin-adhesive interface than an etch-and-rinse adhesive. Forty-eight composite-dentin short rod chevron-notched specimens were prepared. XP Bond and G Bond were used as adhesives. After 7 days in distilled water at 37°C, each specimen was tested (cross-head speed=0.05 mm/min). Fractured surfaces were inspected and characterized as interfacial failures, composite failures or a combination of interfacial and composite failures. The fracture toughness values (K(IC)) of the two adhesives were compared (Student's t-test and Weibull statistics). Of the specimens bonded with XP Bond, 50% failed at the dentin-adhesive interface, 42% at both the dentin-adhesive and composite interface and 8% in the composite alone. Of the specimens bonded with G Bond, 41% failed at the dentin-adhesive interface, 53% at both the dentin-adhesive and composite interface and 6% in the composite alone. The K(IC) values of the two adhesives differed significantly (pBond had a K(IC) of 0.77±0.11 MNm(-3/2) (n=17), while G Bond a K(IC) of 0.62±0.21 MNm(-3/2) (n=12). The high percentage of mixed failures did not support the hypothesis that the dentin-adhesive interface is clearly less resistant to fracture than the adhesive-composite interface. The finding that cracks occurred in 6-8% in the composite suggests that defects within the composite or at the adhesive-composite interface are important variables to consider in adhesion testing. Copyright © 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  18. Transient adhesion of neutrophils to endothelium.

    Science.gov (United States)

    Lo, S K; Detmers, P A; Levin, S M; Wright, S D

    1989-05-01

    Fluorescently labeled polymorphonuclear leukocytes (PMN) were used to measure adhesion to human umbilical vein endothelial cells (EC) cultured in vitro. Stimulation of PMN with phorbol dibutyrate (PDB), TNF, or C5a caused an increase in adhesion followed by a return to prestimulation levels of adhesion of longer times of incubation. Maximal adhesion of PMN to EC occurred rapidly in response to C5a (5 min) and more slowly with TNF or PDB (15 min). PMN stimulated to adhere with C5a detached from EC by 15 min. PMN from CD11/CD18-deficient patients and PMN incubated with anti-CD18 mAbs failed to bind to EC despite maximal stimulation. Anti-CD11a/CD18 and anti-CD11b/CD18 each partially inhibited adhesion, and a combination of these two reagents completely blocked adhesion. The adhesion we measured was therefore completely dependent on CD11/CD18, and CD11a/CD18 and CD11b/CD18 each contributed to adhesion. Stimuli that enhanced adhesion of PMN to EC also enhanced expression of CD11b/CD18 on the cell surface, but the time course of expression correlated poorly with changes in adhesivity. To determine if changes in the expression of CD11b/CD18 are necessary for the changes in adhesivity, we used enucleate cytoplasts that did not increase expression of CD11b/CD18. Cytoplasts showed a normal rise and fall in adhesivity in response to PDB. We conclude that the transient adhesion of stimulated PMN to naive EC is regulated by changes in the nature of existing CD11/CD18 molecules on the PMN surface. Changes in expression of CD11b/CD18 may contribute to enhancement of adhesivity, but a definite role for this phenomenon has yet to be established.

  19. Polymer Claw: Instant Underwater Adhesive

    Science.gov (United States)

    2012-10-23

    Prescribed by ANSI Std. Z39.18 REDD -2012-413 POLYMER CLAW: INSTANT UNDERWATER ADHESIVE Progress Report #8 Prepared for: Dr. Reggie Beach...Report: October 23, 2012 2.ol X\\oZ\\olc] The Johns Hopkins University Applied Physics Laboratory 11100 Johns Hopkins Rd, Laurel, MD 20723 REDD -2012...2- 10/23/12 The Johns Hopkins University Applied Physics Laboratory 11100 Johns Hopkins Rd, Laurel, MD 20723 REDD -2012-413 1 Summary When

  20. Syndecans, signaling, and cell adhesion

    DEFF Research Database (Denmark)

    Couchman, J R; Woods, A

    1996-01-01

    Syndecans are transmembrane proteoglycans which can participate in diverse cell surface interactions, involving extracellular matrix macromolecules, growth factors, protease inhibitors, and even viral entry. Currently, all extracellular interactions are believed to be mediated by distinct...... structures within the heparan sulfate chains, leaving the roles of chondroitin sulfate chains and extracellular portion of the core proteins to be elucidated. Evidence that syndecans are a class of receptor involved in cell adhesion is mounting, and their small cytoplasmic domains may link...

  1. A review of our development of dental adhesives--effects of radical polymerization initiators and adhesive monomers on adhesion.

    Science.gov (United States)

    Ikemura, Kunio; Endo, Takeshi

    2010-03-01

    This paper reviews the development of dental adhesives by collating information of related studies from original scientific papers, reviews, and patent literatures. Through our development, novel radical polymerization initiators, adhesive monomers, and microcapsules were synthesized, and their effects on adhesion were investigated. It was found that 5-monosubstituted barbituric acid (5-MSBA)-containing ternary initiators in conjunction with adhesive monomers contributed to effective adhesion with good polymerization reactivity. Several kinds of novel adhesive monomers bearing carboxyl group, phosphonic acid group or sulfur-containing group were synthesized, and investigated their multi-purpose bonding functions. It was suggested that the flexible methylene chain in the structure of adhesive monomers played a pivotal role in their enhanced bonding durability. It was found that the combination of acidic monomers with sulfur-containing monomer markedly improved adhesion to enamel, dentin, porcelain, alumina, zirconia, non-precious metals and precious metals. A new poly(methyl methacrylate) (PMMA)-type adhesive resin comprising microencapsulated polymerization initiators was also found to exhibit both good formulation stability and excellent adhesive property.

  2. Modeling of Sylgard Adhesive Strength

    Energy Technology Data Exchange (ETDEWEB)

    Stevens, Ralph Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2015-02-03

    Sylgard is the name of a silicone elastomeric potting material manufactured by Dow Corning Corporation.1 Although the manufacturer cites its low adhesive strength as a feature of this product, thin layers of Sylgard do in fact have a non-negligible strength, which has been measured in recent tensile and shear debonding tests. The adhesive strength of thin layers of Sylgard potting material can be important in applications in which components having signi cantly di erent thermal expansion properties are potted together, and the potted assembly is subjected to temperature changes. The tensile and shear tractions developed on the potted surfaces of the components can cause signi cant internal stresses, particularly for components made of low-strength materials with a high area-to-volume ratio. This report is organized as follows: recent Sylgard debonding tests are rst brie y summarized, with particular attention to the adhesion between Sylgard and PBX 9501, and also between Sylgard and aluminum. Next, the type of numerical model that will be used to simulate the debonding behavior exhibited in these tests is described. Then the calibration of the debonding model will be illustrated. Finally, the method by which the model parameters are adjusted (scaled) to be applicable to other, non- tested bond thicknesses is summarized, and all parameters of the model (scaled and unscaled) are presented so that other investigators can reproduce all of the simulations described in this report as well as simulations of the application of interest.

  3. Culinary Medicine-Jalebi Adhesions.

    Science.gov (United States)

    Kapoor, Vinay K

    2016-02-01

    Culinary terms have been used to describe anatomy (bean-shaped kidneys), pathology (strawberry gall bladder), clinical signs (café-au-lait spots), radiological images (sausage-shaped pancreas), etc. While Indian cuisine is popular all over the world, no Indian dish finds mention in medical terminology. In intra-abdominal adhesions, sometimes, the intestinal loops are so densely adherent that it is difficult to make out proximal from distal and it is impossible to separate them without injuring the bowel resulting in spill of contents-resection is the only option (Fig. 1). Jalebi, an Indian dessert, has a single long tubular strip of fried batter filled with sugary syrup so intertwined that it is impossible to discern its ends; if broken, the syrup spills out-the best way to relish it is to chew the whole piece (Fig. 2). Because of these similarities between them, I propose to name dense intra-abdominal adhesions as 'jalebi adhesions.'

  4. Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

    Directory of Open Access Journals (Sweden)

    Taysa Bervian Bassani

    2015-07-01

    Full Text Available Parkinson’s disease (PD is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.

  5. Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Amin Mottahedin

    2017-07-01

    Full Text Available The brain is a plastic organ where both the intrinsic CNS milieu and extrinsic cues play important roles in shaping and wiring neural connections. The perinatal period constitutes a critical time in central nervous system development with extensive refinement of neural connections, which are highly sensitive to fetal and neonatal compromise, such as inflammatory challenges. Emerging evidence suggests that inflammatory cells in the brain such as microglia and astrocytes are pivotal in regulating synaptic structure and function. In this article, we will review the role of glia cells in synaptic physiology and pathophysiology, including microglia-mediated elimination of synapses. We propose that activation of the immune system dynamically affects synaptic organization and function in the developing brain. We will discuss the role of neuroinflammation in altered synaptic plasticity following perinatal inflammatory challenges and potential implications for neurodevelopmental and neurodegenerative disorders.

  6. Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

    Directory of Open Access Journals (Sweden)

    Guangbing Wei

    2016-09-01

    Full Text Available Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control. On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson’s trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA, interleukin-6 (IL-6, and transforming growth factor β1 (TGF-β1 in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs. Western blotting was performed to examine the expression of the TGF-β1, fibrinogen and α-smooth muscle actin (α-SMA proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor α (TNF-α and TGF-β1 in the abdominal fluid. The

  7. Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

    Science.gov (United States)

    Wei, Guangbing; Zhou, Cancan; Wang, Guanghui; Fan, Lin; Wang, Kang; Li, Xuqi

    2016-01-01

    Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF) has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA) gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control). On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson’s trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA), interleukin-6 (IL-6), and transforming growth factor β1 (TGF-β1) in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs). Western blotting was performed to examine the expression of the TGF-β1, fibrinogen and α-smooth muscle actin (α-SMA) proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor α (TNF-α) and TGF-β1 in the abdominal fluid. The expression

  8. Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available Long-term consequences of traumatic brain injury (TBI are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD, yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long

  9. Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder.

    Science.gov (United States)

    Kim, WooJin; Zekas, Erin; Lodge, Robert; Susan-Resiga, Delia; Marcinkiewicz, Edwidge; Essalmani, Rachid; Mihara, Koichiro; Ramachandran, Rithwik; Asahchop, Eugene; Gelman, Benjamin; Cohen, Éric A; Power, Christopher; Hollenberg, Morley D; Seidah, Nabil G

    2015-11-01

    The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. Non-celiac gluten sensitivity triggers gut dysbiosis, neuroinflammation, gut-brain axis dysfunction, and vulnerability for dementia.

    Science.gov (United States)

    Daulatzai, Mak Adam

    2015-01-01

    The non-celiac gluten sensitivity (NCGS) is a chronic functional gastrointestinal disorder which is very common world wide. The human gut harbors microbiota which has a wide variety of microbial organisms; they are mainly symbiotic and important for well being. However, "dysbiosis" - i.e. an alteration in normal commensal gut microbiome with an increase in pathogenic microbes, impacts homeostasis/health. Dysbiosis in NCGS causes gut inflammation, diarrhea, constipation, visceral hypersensitivity, abdominal pain, dysfunctional metabolic state, and peripheral immune and neuro-immune communication. Thus, immune-mediated gut and extra-gut dysfunctions, due to gluten sensitivity with comorbid diarrhea, may last for decades. A significant proportion of NCGS patients may chronically consume alcohol, non-steroidal anti-inflammatory drugs, and fatty diet, as well as suffer from various comorbid disorders. The above pathophysiological substrate and dysbiosis are underpinned by dysfunctional bidirectional "Gut-Brain Axis" pathway. Pathogenic gut microbiota is known to upregulate gut- and systemic inflammation (due to lipopolysaccharide from pathogenic bacteria and synthesis of pro-inflammatory cytokines); they enhance energy harvest, cause obesity, insulin resistance, and dysfunctional vago-vagal gut-brain axis. Conceivably, the above cascade of pathology may promote various pathophysiological mechanisms, neuroinflammation, and cognitive dysfunction. Hence, dysbiosis, gut inflammation, and chronic dyshomeostasis are of great clinical relevance. It is argued here that we need to be aware of NCGS and its chronic pathophysiological impact. Therapeutic measures including probiotics, vagus nerve stimulation, antioxidants, alpha 7 nicotinic receptor agonists, and corticotropin-releasing factor receptor 1 antagonist may ameliorate neuroinflammation and oxidative stress in NCGS; they may therefore, prevent cognitive dysfunction and vulnerability to Alzheimer's disease.

  11. Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice

    Directory of Open Access Journals (Sweden)

    Choi Youkyung

    2011-02-01

    Full Text Available Abstract Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects.

  12. Interleukin-10 inhibits neuroinflammation-mediated apoptosis of ventral mesencephalic neurons via JAK-STAT3 pathway.

    Science.gov (United States)

    Zhu, Yan; Liu, Zhan; Peng, Yu-Ping; Qiu, Yi-Hua

    2017-09-01

    Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease. Interleukin (IL)-10 is one of the most important and best anti-inflammatory cytokines. The objective of this report is to investigate whether IL-10 has any role in protecting ventral mesencephalic (VM) neurons in in vitro model of neuroinflammation. In this study, primary neuron-enriched culture was prepared from the VM tissues of E14 embryos of rats. The cells were pretreated with IL-10 (15 or 50ng/mL) for 1h followed by lipopolysaccharide (LPS, 50ng/mL) application. We found LPS induced neuronal apoptosis and loss while pretreatment with IL-10 reduced neuronal damage after exposure of LPS toxicity. Furthermore, signal transduction pathways related to IL-10 in VM neurons were studied in inflammatory condition. We used both shRNA and pharmacologic inhibition to determine the role of the IL-10 receptor (IL-10R) and its downstream signaling pathways in LPS-induced VM neuronal toxicity. Silence of the IL-10R gene in VM neurons abolished IL-10 mediated protection and the properties of anti-inflammatory and anti-apoptosis. IL-10 also induced phosphorylation of signal transducer and activator of transcription (STAT) 3 in VM neurons. Pretreatment with the specific Janus kinase (JAK) inhibitor reduced STAT3 phosphorylation and blocked IL-10 mediated protection against LPS. These findings suggest that IL-10 provides neuroprotection by acting via IL-10R and its down-stream JAK-STAT3 signal pathways in VM neurons. Copyright © 2017. Published by Elsevier B.V.

  13. Embryonic Stem Cell Markers

    Directory of Open Access Journals (Sweden)

    Lan Ma

    2012-05-01

    Full Text Available Embryonic stem cell (ESC markers are molecules specifically expressed in ES cells. Understanding of the functions of these markers is critical for characterization and elucidation for the mechanism of ESC pluripotent maintenance and self-renewal, therefore helping to accelerate the clinical application of ES cells. Unfortunately, different cell types can share single or sometimes multiple markers; thus the main obstacle in the clinical application of ESC is to purify ES cells from other types of cells, especially tumor cells. Currently, the marker-based flow cytometry (FCM technique and magnetic cell sorting (MACS are the most effective cell isolating methods, and a detailed maker list will help to initially identify, as well as isolate ESCs using these methods. In the current review, we discuss a wide range of cell surface and generic molecular markers that are indicative of the undifferentiated ESCs. Other types of molecules, such as lectins and peptides, which bind to ESC via affinity and specificity, are also summarized. In addition, we review several markers that overlap with tumor stem cells (TSCs, which suggest that uncertainty still exists regarding the benefits of using these markers alone or in various combinations when identifying and isolating cells.

  14. [Study of skin markers for magnetic resonance imaging examinations].

    Science.gov (United States)

    Takatsu, Yasuo; Umezaki, Yoshie; Miyati, Tosiaki; Yamamura, Kenichirou

    2013-03-01

    In magnetic resonance imaging (MRI), skin markers are used as a landmark in order to make plans for examinations. However, there isn't a lot of research about the material and shape of skin markers. The skin marker's essential elements are safety, good cost performance, high signal intensity for T1 weighted image (T1WI) and T2 weighted image (T2WI), and durable. In order to get a high signal-to-noise ratio (SNR) of T1WI and T2WI, baby oil, salad oil and olive oil were chosen, because these materials were easy to obtain and safe for the skin. The SNR of baby oil was the best. Baby oil was injected into the infusion tube, and the tube was solvent welded and cut by a heat sealer. In order to make ring shaped skin markers, both ends of the tube were stuck with adhesive tape. Three different diameters of markers were made (3, 5, 10 cmψ). Ring shaped skin markers were put on to surround the examination area, therefore, the edge of the examination area could be seen at every cross section. Using baby oil in the ring shaped infusion tube is simple, easy, and a highly useful skin marker.

  15. Carbon nanotube dry adhesives with temperature-enhanced adhesion over a large temperature range

    OpenAIRE

    Xu, Ming; Du, Feng; Ganguli, Sabyasachi; Roy, Ajit; Dai, Liming

    2016-01-01

    Conventional adhesives show a decrease in the adhesion force with increasing temperature due to thermally induced viscoelastic thinning and/or structural decomposition. Here, we report the counter-intuitive behaviour of carbon nanotube (CNT) dry adhesives that show a temperature-enhanced adhesion strength by over six-fold up to 143?N?cm?2 (4?mm ? 4?mm), among the strongest pure CNT dry adhesives, over a temperature range from ?196 to 1,000??C. This unusual adhesion behaviour leads to temperat...

  16. Autism Spectrum Disorders May Be Due to Cerebral Toxoplasmosis Associated with Chronic Neuroinflammation Causing Persistent Hypercytokinemia that Resulted in an Increased Lipid Peroxidation, Oxidative Stress, and Depressed Metabolism of Endogenous and Exogenous Substances

    Science.gov (United States)

    Prandota, Joseph

    2010-01-01

    Worldwide, approximately 2 billion people are chronically infected with "Toxoplasma gondii" with largely yet unknown consequences. Patients with autism spectrum disorders (ASD) similarly as mice with chronic toxoplasmosis have persistent neuroinflammation, hypercytokinemia with hypermetabolism associated with enhanced lipid peroxidation, and…

  17. Human climbing with efficiently scaled gecko-inspired dry adhesives

    OpenAIRE

    Hawkes, Elliot W.; Eason, Eric V.; Christensen, David L.; Cutkosky, Mark R.

    2015-01-01

    Since the discovery of the mechanism of adhesion in geckos, many synthetic dry adhesives have been developed with desirable gecko-like properties such as reusability, directionality, self-cleaning ability, rough surface adhesion and high adhesive stress. However, fully exploiting these adhesives in practical applications at different length scales requires efficient scaling (i.e. with little loss in adhesion as area grows). Just as natural gecko adhesives have been used as a benchmark for syn...

  18. The urine marker test

    DEFF Research Database (Denmark)

    Elbe, Anne-Marie; Jensen, Stine Nylandsted; Elsborg, Peter

    2016-01-01

    of this new method via two questionnaires (n = 253). Furthermore, a third study (n = 91) investigated whether ingestion of the marker can identify the urine as coming from a specific person and whether the marker interferes with the detection of prohibited substances. RESULTS AND CONCLUSIONS: The results...... indicate that this new method finds wide acceptance both from athletes who have only heard about the procedure and those who have actually tested the new method. Furthermore, the marker, which can identify urine as coming from a specific person, does not interfere with the detection of prohibited...... that athletes are actually delivering their own urine. A method that can be used to alleviate the negative impact of a supervised urination procedure and which can also identify urine as coming from a specific athlete is the urine marker test. Monodisperse low molecular weight polyethylene glycols (PEGs...

  19. VT Roadside Historic Markers

    Data.gov (United States)

    Vermont Center for Geographic Information — Roadside Historic Site Marker program has proven an effective way to commemorate Vermont’s many people, events, and places of regional, statewide, or national...

  20. Proteomic dataset of the sea urchin Paracentrotus lividus adhesive organs and secreted adhesive

    Directory of Open Access Journals (Sweden)

    Nicolas Lebesgue

    2016-06-01

    Full Text Available Sea urchins have specialized adhesive organs called tube feet, which mediate strong but reversible adhesion. Tube feet are composed by a disc, producing adhesive and de-adhesive secretions for substratum attachment, and a stem for movement. After detachment the secreted adhesive remains bound to the substratum as a footprint. Recently, a label-free quantitative proteomic approach coupled with the latest mass-spectrometry technology was used to analyze the differential proteome of Paracentrotus lividus adhesive organ, comparing protein expression levels in the tube feet adhesive part (the disc versus the non-adhesive part (the stem, and also to profile the proteome of the secreted adhesive (glue. This data article contains complementary figures and results related to the research article “Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: a quantitative proteomics approach” (Lebesgue et al., 2016 [1]. Here we provide a dataset of 1384 non-redundant proteins, their fragmented peptides and expression levels, resultant from the analysis of the tube feet differential proteome. Of these, 163 highly over-expressed tube feet disc proteins (>3-fold, likely representing the most relevant proteins for sea urchin reversible adhesion, were further annotated in order to determine the potential functions. In addition, we provide a dataset of 611 non-redundant proteins identified in the secreted adhesive proteome, as well as their functional annotation and grouping in 5 major protein groups related with adhesive exocytosis, and microbial protection. This list was further analyzed to identify the most abundant protein groups and pinpoint putative adhesive proteins, such as Nectin, the most abundant adhesive protein in sea urchin glue. The obtained data uncover the key proteins involved in sea urchins reversible adhesion, representing a step forward to the development of new wet-effective bio-inspired adhesives.

  1. Proteomic dataset of the sea urchin Paracentrotus lividus adhesive organs and secreted adhesive.

    Science.gov (United States)

    Lebesgue, Nicolas; da Costa, Gonçalo; Ribeiro, Raquel Mesquita; Ribeiro-Silva, Cristina; Martins, Gabriel G; Matranga, Valeria; Scholten, Arjen; Cordeiro, Carlos; Heck, Albert J R; Santos, Romana

    2016-06-01

    Sea urchins have specialized adhesive organs called tube feet, which mediate strong but reversible adhesion. Tube feet are composed by a disc, producing adhesive and de-adhesive secretions for substratum attachment, and a stem for movement. After detachment the secreted adhesive remains bound to the substratum as a footprint. Recently, a label-free quantitative proteomic approach coupled with the latest mass-spectrometry technology was used to analyze the differential proteome of Paracentrotus lividus adhesive organ, comparing protein expression levels in the tube feet adhesive part (the disc) versus the non-adhesive part (the stem), and also to profile the proteome of the secreted adhesive (glue). This data article contains complementary figures and results related to the research article "Deciphering the molecular mechanisms underlying sea urchin reversible adhesion: a quantitative proteomics approach" (Lebesgue et al., 2016) [1]. Here we provide a dataset of 1384 non-redundant proteins, their fragmented peptides and expression levels, resultant from the analysis of the tube feet differential proteome. Of these, 163 highly over-expressed tube feet disc proteins (>3-fold), likely representing the most relevant proteins for sea urchin reversible adhesion, were further annotated in order to determine the potential functions. In addition, we provide a dataset of 611 non-redundant proteins identified in the secreted adhesive proteome, as well as their functional annotation and grouping in 5 major protein groups related with adhesive exocytosis, and microbial protection. This list was further analyzed to identify the most abundant protein groups and pinpoint putative adhesive proteins, such as Nectin, the most abundant adhesive protein in sea urchin glue. The obtained data uncover the key proteins involved in sea urchins reversible adhesion, representing a step forward to the development of new wet-effective bio-inspired adhesives.

  2. Adhesion and wear resistance of materials

    Science.gov (United States)

    Buckley, D. H.

    1986-01-01

    Recent studies into the nature of bonding at the interface between two solids in contact or a solid and deposited film have provided a better understanding of those properties important to the adhesive wear resistance of materials. Analytical and experimental progress are reviewed. For simple metal systems the adhesive bond forces are related to electronic wave function overlap. With metals in contact with nonmetals, molecular-orbital energy, and density of states, respectively can provide insight into adhesion and wear. Experimental results are presented which correlate adhesive forces measured between solids and the electronic surface structures. Orientation, surface reconstruction, surface segregation, adsorption are all shown to influence adhesive interfacial strength. The interrelationship between adhesion and the wear of the various materials as well as the life of coatings applied to substrates are discussed. Metallic systems addressed include simple metals and alloys and these materials in contact with themselves, both oxide and nonoxide ceramics, diamond, polymers, and inorganic coating compounds, h as diamondlike carbon.

  3. Improving controllable adhesion on both rough and smooth surfaces with a hybrid electrostatic/gecko-like adhesive

    OpenAIRE

    Ruffatto, Donald; Parness, Aaron; Spenko, Matthew

    2014-01-01

    This paper describes a novel, controllable adhesive that combines the benefits of electrostatic adhesives with gecko-like directional dry adhesives. When working in combination, the two technologies create a positive feedback cycle whose adhesion, depending on the surface type, is often greater than the sum of its parts. The directional dry adhesive brings the electrostatic adhesive closer to the surface, increasing its effect. Similarly, the electrostatic adhesion helps engage more of the di...

  4. Testing thin film adhesion strength acoustically

    Science.gov (United States)

    Madanshetty, Sameer I.; Wanklyn, Kevin M.; Ji, Hang

    2004-05-01

    A new method of measuring the adhesion strength of thin films to their substrates is reported. The method is based on an analogy with the common tensile test of materials. This is an acoustic method that uses acoustic microcavitation to bring about controlled erosion of the thin film. Based on the insonification pressure and the time to complete erosion, the adhesion strength is assessed. The measurements correctly rank order a set of thin film samples of known adhesion strengths.

  5. [Adhesive capsulitis of the shoulder].

    Science.gov (United States)

    Revel, M; Ghanem, N

    1999-09-01

    Adhesive capsulitis is a painful stiff shoulder due to the thickening of the capsule and synovium. The main observed changes are hyperhaemia of the synovium and a capsular fibrosis similar to that of Dupuytren's disease. Stiffness involves mainly flexion, lateral rotation and abduction. In most cases, a spontaneous healing is observed within 12 to 30 months. When the capsulitis is disabling and pain still present, a joint distension followed by rehabilitation can be indicated. When the disability is important and mainly due to stiffness, a manipulation under anesthesia with or without arthroscopic release of soft tissues can be indicated.

  6. Adhesive Strength of dry Adhesive Structures Depending on the Thickness of Metal Coating

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gyu Hye; Kwon, Da Som; Kim, Mi Jung; Kim, Su Hee; Yoon, Ji Won; An, Tea Chang; Hwang, Hui Yun [Andong National Univ., Andong (Korea, Republic of)

    2016-07-15

    Recently, engineering applications have started to adopt solutions inspired by nature. The peculiar adhesive properties of gecko skin are an example, as they allow the animal to move freely on vertical walls and even on ceilings. The high adhesive forces between gecko feet and walls are due to the hierarchical microscopical structure of the skin. In this study, the effect of metal coatings on the adhesive strength of synthetic, hierarchically structured, dry adhesives was investigated. Synthetic dry adhesives were fabricated using PDMS micro-molds prepared by photolithography. Metal coatings on synthetic dry adhesives were formed by plasma sputtering. Adhesive strength was measured by pure shear tests. The highest adhesion strengths were found with coatings composed of 4 nm thick layers of Indium, 8 nm thick layers of Zinc and 6 nm thick layers of Gold, respectively.

  7. Influence of composition on the adhesive strength and initial viscosity of denture adhesives.

    Science.gov (United States)

    Han, Jian-min; Hong, Guang; Hayashida, Kentaro; Maeda, Takeshi; Murata, Hiroshi; Sasaki, Keiichi

    2014-01-01

    To investigate the effect of composition on the initial viscosity and adhesive strength between denture adhesives and the denture base. Two types of water-soluble polymers (methoxy ethylene maleic anhydride copolymer [PVM-MA] and sodium carboxymethyl cellulose [CMC]) were used. Samples were divided into three groups. Group 1 contained only PVM-MA; Group 2 contained only CMC; and Group 3 contained PVM-MA and CMC. The initial viscosity and adhesive strength were measured. For Group 1, the initial viscosity increased significantly as PVM-MA content increased. The adhesive strength of Group 1 lasted longer than Group 2. The adhesive strength of Group 3 varied greatly. The ratio of CMC and PVM-MA has a significant effect on the initial viscosity and adhesive strength of denture adhesives. Our results suggest that it is possible to improve the durability of a denture adhesive by combining different water-soluble polymers.

  8. An experimental study on adhesive or anti-adhesive, bio-inspired experimental nanomaterials

    National Research Council Canada - National Science Library

    Lepore, Emiliano; Pugno, Nicol

    The proposed book aims to better understand some of the most challenging and disputed topics that could be found in nature, such as adhesive, anti-adhesive or strong mechanisms in plants or animals...

  9. Macrophages migrate in an activation-dependent manner to chemokines involved in neuroinflammation

    Science.gov (United States)

    2014-01-01

    Background In neuroinflammatory diseases, macrophages can play a dual role in the process of tissue damage, depending on their activation status (M1 / M2). M1 macrophages are considered to exert damaging effects to neurons, whereas M2 macrophages are reported to aid regeneration and repair of neurons. Their migration within the central nervous system may be of critical importance in the final outcome of neurodegeneration in neuroinflammatory diseases e.g. multiple sclerosis (MS). To provide insight into this process, we examined the migratory capacity of human monocyte-derived M1 and M2 polarised macrophages towards chemoattractants, relevant for neuroinflammatory diseases like MS. Methods Primary cultures of human monocyte-derived macrophages were exposed to interferon gamma and lipopolysaccharide (LPS) to evoke proinflammatory (M1) activation or IL-4 to evoke anti-inflammatory (M2) activation. In a TAXIScan assay, migration of M0, M1 and M2 towards chemoattractants was measured and quantified. Furthermore the adhesion capacity and the expression levels of integrins as well as chemokine receptors of M0, M1 and M2 were assessed. Alterations in cell morphology were analysed using fluorescent labelling of the cytoskeleton. Results Significant differences were observed between M1 and M2 macrophages in the migration towards chemoattractants. We show that M2 macrophages migrated over longer distances towards CCL2, CCL5, CXCL10, CXCL12 and C1q compared to non-activated (M0) and M1 macrophages. No differences were observed in the adhesion of M0, M1 and M2 macrophages to multiple matrix components, nor in the expression of integrins and chemokine receptors. Significant changes were observed in the cytoskeleton organization upon stimulation with CCL2, M0, M1 and M2 macrophages adopt a spherical morphology and the cytoskeleton is rapidly rearranged. M0 and M2 macrophages are able to form filopodia, whereas M1 macrophages only adapt a spherical morphology. Conclusions

  10. Magnetic resonance imaging of navicular bursa adhesions.

    Science.gov (United States)

    Holowinski, Maureen E; Solano, Mauricio; Maranda, Louise; García-López, José M

    2012-01-01

    Adhesions occur in the navicular bursa between the deep digital flexor tendon (DDFT) and other structures. Our objectives were to describe the appearance of navicular bursa adhesions on high-field magnetic resonance (MR) images, to compare these findings to findings at navicular bursoscopy, and to determine the prevalence of lesions in the remainder of the podotrochlear apparatus. Sixteen forelimbs from 14 horses that underwent MR imaging and navicular bursoscopy were evaluated. Adhesions were considered type 1 when characterized by a discontinuity in the navicular bursa fluid signal between two structures, type 2 when the navicular bursa fluid signal was disrupted and ill-defined tissue was present between two structures, and type 3 when the fluid signal was disrupted and well-defined tissue was present between two structures. Twenty-six adhesions were suspected on MR images and nineteen were visualized at surgery. The positive predictive value was 50% for type 1 adhesions, 67% for type 2 adhesions, and 100% for type 3 adhesions. Additional lesions were detected in the navicular bursa in 15 limbs, the DDFT in 13, the navicular bone in 15, the collateral sesamoidean ligaments in 9, and the distal sesamoidean impar ligament in 8. A discontinuity in the navicular bursa fluid signal with well-defined tissue between two structures detected on high-field MR images is diagnostic for a navicular bursa adhesion. Additional lesions in the podotrochlear apparatus are common in horses with navicular bursa adhesions. © 2012 Veterinary Radiology & Ultrasound.

  11. Familial adhesive arachnoiditis associated with syringomyelia

    National Research Council Canada - National Science Library

    Pasoglou, V; Janin, N; Tebache, M; Tegos, T J; Born, J D; Collignon, L

    2014-01-01

    Adhesive arachnoiditis is a rare condition, often complicated by syringomyelia. This pathologic entity is usually associated with prior spinal surgery, spinal inflammation or infection, and hemorrhage...

  12. The development of aerospace polyimide adhesives

    Science.gov (United States)

    St.clair, A. K.; St.clair, T. L.

    1983-01-01

    Few materials are available which can be used as aerospace adhesives at temperatures in the range of 300 C. The Materials Division at NASA-Langley Research Center developed several high temperature polyimide adhesives to fulfill the stringent needs of current aerospace programs. These adhesives are the result of a decade of basic research studies on the structure property relationships of both linear and addition aromatic polyimides. The development of both in house and commercially available polyimides is reviewed with regards to their potential for use as aerospace adhesives.

  13. Autologous fibrin adhesive in experimental tubal anastomosis.

    Science.gov (United States)

    Rajaram, S; Rusia, U; Agarwal, S; Agarwal, N

    1996-01-01

    To evaluate autologous fibrin in rabbit oviduct anastomosis versus 7-0 vikryl, a conventional suture material used in tubal anastomosis. Thrombin was added to the autologous fibrinogen at the site of anastomosis to obtain a tissue adhesive. The anastomotic time, pregnancy rate, and litter size were evaluated. Three months later, a relaparotomy was done to evaluate patency and degree of adhesions, and a tubal biopsy was taken from the site of anastomosis. Analysis of results showed a statistically significant (P < .001) shortened anastomotic time and superior histopathological union in the tissue adhesive group. Patency rate, pregnancy rate, and degree of adhesions were comparable in both groups.

  14. Ultramorphology of pre-treated adhesive interfaces between self-adhesive resin cement and tooth structures

    OpenAIRE

    Pereira,Carolina Nemesio de Barros; DALEPRANE,Bruno; MIRANDA,Giovani Lana Peixoto de; Magalhães,Cláudia Silami de; Moreira, Allyson Nogueira

    2017-01-01

    Abstract Introduction Convencional resin cements can be used in combination with a total-etch system in a conventional mode or as self-adhesive resin cements. The latter are less technique sensitive and able to bond to dental tissues without previous treatment or adhesive layer and requires only a single step to be applied to dental structures. Objective To compare qualitatively the adhesive interfaces of two self-adhesive resin cements and one conventional resin cement after different toot...

  15. Adhesion performance of new hydrolytically stable one-component self-etching enamel/dentin adhesives.

    Science.gov (United States)

    Salz, Ulrich; Bock, Thorsten

    2010-02-01

    To demonstrate that hydrolytically stable methacrylamide monomers allow one-component self-etching adhesives with comparable adhesive properties and better storage stability than hitherto available methyacrylate-based adhesive formulations. The shear bond strength and storage stability of the new one-component self-etching, methacrylamide-based adhesive AdheSE One F (Ivoclar Vivadent) to enamel and dentin was compared to the methacrylate-based Clearfil S3 Bond (Kuraray), G-Bond (GC), Hybrid Bond (Sun Medical), iBond (Heraeus Kulzer), Optibond All In One (Sybron-Kerr), and the methacrylamide-based Xeno V (Dentsply). Hydrolytic stability and adhesive performance of these adhesives was evaluated by accelerated aging at 42 degrees C over 16 weeks and monthly assessment of shear bond strength to dentin. The null hypothesis was that the bond strength of one-bottle self-etching dental adhesives is independent of storage duration and that, disregarding their higher stability against hydrolysis, methacrylamide- based materials offer performance beyond shelf-life time, comparable to methacrylate-based adhesives. Statistical analysis included 1-way-ANOVA and the Tukey-B post-hoc test (p AdheSE One F) to 16.6 MPa (iBond) and on dentin from 36.1 MPa (Optibond All In One) to 20.5 MPa (G-Bond). During accelerated aging, methacrylate-based adhesives with a pH AdheSE One F and Xeno V were stable for 16 weeks regarding shear bond strength to dentin. The shelf life of one-component self-etching adhesives is determined by their chemical composition. In conventional methacrylate-based adhesives, the inherently acidic environment of such formulations leads to monomer degradation due to hydrolysis. In contrast, methacrylamide-based adhesives are stable to aqueous acid and exhibit much superior storage stability without monomer degradation-related losses in adhesion performance.

  16. Adhesion molecules, chemokines and matrix metallo-proteinases response after albendazole and albendazole plus steroid therapy in swine neurocysticercosis.

    Science.gov (United States)

    Singh, Satyendra K; Prasad, Kashi N; Singh, Aloukick K; Gupta, Kamlesh K; Singh, Amrita; Tripathi, Mukesh; Gupta, Rakesh K

    2017-11-01

    The treatment of neurocysticercosis (NCC) varies with location, number and stage of the Taenia solium cysticerci (cysts). Albendazole (ABZ) effectively kills cysticerci, and subsequently induces neuro-inflammation facilitated by leukocyte infiltration. We hypothesize that immune response varies around drug responder (degenerating/dying) and non-responder (viable) cysts after ABZ and ABZ plus steroid (ABZS) therapy, which may determine the disease pathogenesis. Twenty cysticercotic swine were treated with ABZ (n = 10; group1) and ABZS (n = 10; group2). Expression of adhesion molecules, chemokines and matrix metallo-proteinases (MMPs) was measured by qRT-PCR (quantitative reverse transcriptase-polymerase chain reaction) and ELISA. Gelatin gel zymography was performed to detect the activity of MMP-2 and -9. In group1, ABZ therapy induced higher expressions of ICAM-1 (intercellular adhesion molecule-1), VCAM-1 (vascular cell adhesion molecule-1), E-selectin, MCP-1 (monocyte chemotactic protein-1), Eotaxin-1, MIP-1α (macrophage inflammatory protein-1α), RANTES (regulated on activation, normal T cell expressed and secreted), MMP-2 and MMP-9 around ABZ responder (AR) cysts. Three pigs with cyst burdens ≥10 died following ABZ therapy. However, in group2, moderate expressions of ICAM-1, VCAM-1, E-selectin, RANTES and MMP-9 were associated with ABZS responder (ASR), whereas low expressions of these molecules were associated with ABZS non-responder (ASNR) cysts. In conclusion, ABZ alone therapy is not safe since it causes death of pigs due to higher inflammatory immune response around dying cysts. However, combination therapy is an effective treatment regimen even with the high cyst burden. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Effect of inorganic fillers in paper on the adhesion of pressure-sensitive adhesives

    Science.gov (United States)

    Weixu Chen; Xiaoyan Tang; John Considine; Kevin T. Turner

    2011-01-01

    Inorganic fillers are inexpensive materials used to increase the density, smoothness and other properties of paper that are important for printing. In the current study, the adhesion of pressure-sensitive adhesives (PSAs), a common type of adhesive used in labels and tapes, to papers containing varying amounts and types of fillers is investigated. Papers with three...

  18. Repeated mild lateral fluid percussion brain injury in the rat causes cumulative long-term behavioral impairments, neuroinflammation, and cortical loss in an animal model of repeated concussion.

    Science.gov (United States)

    Shultz, Sandy R; Bao, Feng; Omana, Vanessa; Chiu, Charlotte; Brown, Arthur; Cain, Donald Peter

    2012-01-20

    There is growing evidence that repeated brain concussion can result in cumulative and long-term behavioral symptoms, neuropathological changes, and neurodegeneration. Little is known about the factors and mechanisms that contribute to these effects. The current study addresses the need to investigate and better understand the effects of repeated concussion through the development of an animal model. Male Long-Evans rats received 1, 3, or 5 mild lateral fluid percussion injuries or sham injuries spaced 5 days apart. After the final injury, rats received either a short (24 h) or long (8 weeks) post-injury recovery period, followed by a detailed behavioral analysis consisting of tests for rodent anxiety-like behavior, cognition, social behavior, sensorimotor function, and depression-like behavior. Brains were examined immunohistochemically to assess neuroinflammation and cortical damage. Rats given 1, 3, or 5 mild percussion injuries displayed significant short-term cognitive impairments. Rats given repeated mild percussion injuries displayed significantly worse short- and long-term cognitive impairments. Rats given 5 mild percussion injuries also displayed increased anxiety- and depression-like behaviors. Neuropathological analysis revealed short-term neuroinflammation in 3-injury rats, and both short- and long-term neuroinflammation in 5-injury rats. There was also evidence that repeated injuries induced short- and long-term cortical damage. These cumulative and long-term changes are consistent with findings in human patients suffering repeated brain concussion, provide support for the use of repeated mild lateral fluid percussion injuries to study repeated concussion in the rat, and suggest that neuroinflammation may be important for understanding the cumulative and chronic effects of repeated concussion.

  19. T-bet-dependent NKp46+ innate lymphoid cells regulate the onset of TH17-induced neuroinflammation. | Center for Cancer Research

    Science.gov (United States)

    The process by which self-reactive CD4+ T cells infiltrate the central nervous system (CNS) and trigger neuroinflammation is not fully understood. Lazarevic and colleagues show that NKp46+innate lymphoid cells dependent on the transcription factor T-bet are critical mediators in facilitating the entry of autoreactive CD4+ cells of the TH17 subset of helper T cells into the CNS, which leads to autoimmunity. Artwork by Lewis Long.

  20. Design and fabrication of polymer based dry adhesives inspired by the gecko adhesive system

    Science.gov (United States)

    Jin, Kejia

    There has been significant interest in developing dry adhesives mimicking the gecko adhesive system, which offers several advantages compared to conventional pressure sensitive adhesives. Specifically, gecko adhesive pads have anisotropic adhesion properties: the adhesive pads (spatulae) stick strongly when sheared in one direction but are non-adherent when sheared in the opposite direction. This anisotropy property is attributed to the complex topography of the array of fine tilted and curved columnar structures (setae) that bear the spatulae. In this thesis, easy, scalable methods, relying on conventional and unconventional techniques are presented to incorporate tilt in the fabrication of synthetic polymer-based dry adhesives mimicking the gecko adhesive system, which provide anisotropic adhesion properties. In the first part of the study, the anisotropic adhesion and friction properties of samples with various tilt angles to test the validity of a nanoscale tape-peeling model of spatular function are measured. Consistent with the Peel Zone model, samples with lower tilt angles yielded larger adhesion forces. Contact mechanics of the synthetic array were highly anisotropic, consistent with the frictional adhesion model and gecko-like. Based on the original design, a new design of gecko-like dry adhesives was developed which showed superior tribological properties and furthermore showed anisotropic adhesive properties without the need for tilt in the structures. These adhesives can be used to reversibly suspend weights from vertical surfaces (e.g., walls) and, for the first time to our knowledge, horizontal surfaces (e.g., ceilings) by simultaneously and judiciously activating anisotropic friction and adhesion forces. Furthermore, adhesion properties between artificial gecko-inspired dry adhesives and rough substrates with varying roughness are studied. The results suggest that both adhesion and friction forces on a rough substrate depends significantly on the

  1. AN ANALYTICAL STUDY IN ADHESIVE BOWEL OBSTRUCTION

    Directory of Open Access Journals (Sweden)

    Gerald Anand Raja

    2017-04-01

    Full Text Available BACKGROUND Peritoneal adhesions can be defined as abnormal fibrous bands between organs or tissues or both in the abdominal cavity that are normally separated. Adhesions may be acquired or congenital; however, most are acquired as a result of peritoneal injury, the most common cause of which is abdominopelvic surgery. Less commonly, adhesions may form as the result of inflammatory conditions, intraperitoneal infection or abdominal trauma. The extent of adhesion formation varies from one patient to another and is most dependent on the type and magnitude of surgery performed as well as whether any postoperative complications develop. Fortunately, most patients with adhesions do not experience any overt clinical symptoms. For others, adhesions may lead to any one of a host of problems and can be the cause of significant morbidity and mortality. MATERIALS AND METHODS This is a retrospective study of 50 patients admitted in Government Royapettah Hospital with adhesive bowel obstruction between September 2008 to September 2010. All patients were admitted and managed either conservatively or surgically. RESULTS 1. Adhesive bowel disease is the most common cause for bowel obstruction followed by hernias. 2. Increased incidence is noted in females. 3. Increased incidence of adhesions was documented in gynaecological and colorectal surgeries. 4. Below umbilical incisions have higher propensity for adhesion formation. 5. Laparotomies done for infective aetiology have higher adhesion risks. 6. Most of adhesive obstructions can be managed conservatively. 7. Adhesiolysis preferably laparoscopic can be done. For gangrenous bowel resection and anastomosis or ostomy done. 8. Given the above risk factors, adhesive bowel disease can be prevented to a certain extent. CONCLUSION The formation of peritoneal adhesions continues to plague patients, surgeons and society. Although, research in this area is ongoing, there is currently no method that is 100% effective in

  2. Disinfection effect of dental impression tray adhesives.

    Science.gov (United States)

    Bensel, Tobias; Pollak, Rita; Stimmelmayr, Michael; Hey, Jeremias

    2013-03-01

    Iatrogenic infections are serious problems in dental offices. Impression tray adhesives are delivered in glass containers with a fixed brush attached inside the cap. Using the brush for application of the impression tray adhesive on a contaminated impression tray or prostheses, pathogen transmission by replacing the cap with the brush is possible. Bacterial strains (patient strains and in vitro strains) were supervaccinated on Columbia agar. The bacterial solution was diluted with TSB and aerobically grown, and starting concentration was 1 × 10(7) cfu/ml. The stock solution was placed on Columbia agar. Alginate, polyether, and silicon impression tray adhesives were applied to the center of the particular blood agar plates and incubated for 48 h. The expansion of the inhibition zone assays were measured using a microscope. Twenty-one different bacterial strains were selected in the saliva samples of 20 patients. The growth inhibition for alginate impression tray adhesive was 1.1 % (±0.3) of the patient strains. The overgrowth of polyether impression tray adhesive was 30.6 % (±9.3) and for silicon impression tray adhesive 11.8 % (±5.0). In in vitro strains, alginate impression tray adhesive performed an inhibition of 0.7 % (±0.3). The overgrowth of polyether impression tray adhesive was 7.0 % (±1.6) and for silicon impression tray adhesive was 6.5 % (±1.3). Using the fixed brush for application of the impression tray adhesive on multiple patients, a cross-contamination cannot be ruled out. An application of the impression tray adhesive with a pipette and a single-use brush would eliminate the contamination.

  3. Sex-dependent effects of developmental exposure to different pesticides on spatial learning. The role of induced neuroinflammation in the hippocampus.

    Science.gov (United States)

    Gómez-Giménez, Belén; Llansola, Marta; Hernández-Rabaza, Vicente; Cabrera-Pastor, Andrea; Malaguarnera, Michele; Agusti, Ana; Felipo, Vicente

    2017-01-01

    The use of pesticides has been associated with impaired neurodevelopment in children. The aims of this work were to assess: 1) the effects on spatial learning of developmental exposure to pesticides 2) if the effects are sex-dependent and 3) if hippocampal neuroinflammation is associated with the impairment of spatial learning. We analyzed the effects of developmental exposure to four pesticides: chlorpyrifos, carbaryl, endosulfan and cypermethrin. Exposure was from gestational day 7 to post-natal day 21 and spatial learning and memory was assessed when the rats were young adults. The effects of pesticides on spatial learning were pesticide and gender-dependent. Carbaryl did not affect spatial learning in males or females. Endosulfan and chlorpyrifos impaired learning in males but not in females. Cypermethrin improved spatial learning in the Morris water maze both in males and females while impaired learning in the radial maze only in males. Spatial learning ability was lower in control female rats than in males. All pesticides induced neuroinflammation, increasing IL-1b content in the hippocampus and there is a negative correlation between IL-1b levels in the hippocampus and spatial learning. Neuroinflammation would contribute to the effects of pesticides on spatial learning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Ulinastatin suppresses lipopolysaccharide induced neuro-inflammation through the downregulation of nuclear factor-κB in SD rat hippocampal astrocyte

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yuting; Zhao, Lei; Fu, Huiqun [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China); Wu, Yan [Department of Anatomy, Capital Medical University, 100069 Beijing (China); Wang, Tianlong, E-mail: litingliting258@163.com [Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, 100053 Beijing (China)

    2015-03-20

    Astrocyte activation plays a pivotal role in neuroinflammation, which contributes to neuronal damage, so the inhibition of astrocyte activation may alleviate the progression of neurodegeneration. Recent studies have proved that urinary trypsin inhibitor ulinastatin could inhibit NF-kB activation. In our study, the inhibitory effects of ulinastatin on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-reduced primary astrocyte. Our results showed that ulinastatin significantly inhibited LPS-induced astrogliosis, which is measured by MTT and BrdU. Ulinastatin decreased the production of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-1β, it significantly decreased both the mRNA and the protein levels of these pro-inflammatory cytokines and also increased the protein levels of IκB-α binded to NF-κB, which blocked NF-κB translocation to the nucleus and prevented its activity. Our results suggest that ulinastatin is able to inhibit neuroinflammation by interfering with NF-κB signaling. The study provides direct evidence of potential therapy methods of ulinastatin for the treatment of neuroinflammatory diseases. - Highlights: • The anti-inflammatory effect of UTI on hippocampal astrocyte. • UTI showed protective effect on neuroinflammation by the downregulation of NF-κB. • UTI led to expression of cytokines decreased in concentration and time dependence.

  5. Naja sputatrix Venom Preconditioning Attenuates Neuroinflammation in a Rat Model of Surgical Brain Injury via PLA2/5-LOX/LTB4 Cascade Activation.

    Science.gov (United States)

    Wang, Yuechun; Sherchan, Prativa; Huang, Lei; Akyol, Onat; McBride, Devin W; Zhang, John H

    2017-07-14

    Inflammatory preconditioning is a mechanism in which exposure to small doses of inflammatory stimuli prepares the body against future massive insult by activating endogenous protective responses. Phospholipase A2/5-lipoxygenase/leukotriene-B4 (PLA2/5-LOX/LTB4) axis is an important inflammatory signaling pathway. Naja sputatrix (Malayan spitting cobra) venom contains 15% secretory PLA2 of its dry weight. We investigated if Naja sputatrix venom preconditioning (VPC) reduces surgical brain injury (SBI)-induced neuroinflammation via activating PLA2/5-LOX/LTB4 cascade using a partial frontal lobe resection SBI rat model. Naja sputatrix venom sublethal dose was injected subcutaneously for 3 consecutive days prior to SBI. We observed that VPC reduced brain edema and improved neurological function 24 h and 72 h after SBI. The expression of pro-inflammatory mediators in peri-resection brain tissue was reduced with VPC. Administration of Manoalide, a PLA2 inhibitor or Zileuton, a 5-LOX inhibitor with VPC reversed the protective effects of VPC against neuroinflammation. The current VPC regime induced local skin inflammatory reaction limited to subcutaneous injection site and elicited no other toxic effects. Our findings suggest that VPC reduces neuroinflammation and improves outcomes after SBI by activating PLA2/5-LOX/LTB4 cascade. VPC may be beneficial to reduce post-operative neuroinflammatory complications after brain surgeries.

  6. Triggering receptor expressed on myeloid cells 2 knockdown exacerbates aging-related neuroinflammation and cognitive deficiency in senescence-accelerated mouse prone 8 mice.

    Science.gov (United States)

    Jiang, Teng; Yu, Jin-Tai; Zhu, Xi-Chen; Tan, Meng-Shan; Gu, Li-Ze; Zhang, Ying-Dong; Tan, Lan

    2014-06-01

    As a major characteristic of aging process, neuroinflammation is involved in the pathogenesis of several aging-related diseases including Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a newly identified risk gene for AD, which regulates inflammatory process in peripheral tissues via modulating the release of inflammatory cytokines. However, the role of TREM2 in aging-related neuroinflammation, cognitive deficiency, and AD-like neuropathology is unclear so far. Here, we detected the protein levels of TREM2 in brain of 3-, 7-, and 11-month-old senescence-accelerated mouse prone 8 (SAMP8) mice and observed that TREM2 levels were increased during aging process. We then knocked down TREM2 expression in brain of SAMP8 mice by nonviral RNA interference and found a significant increase in proinflammatory cytokines including tumor necrosis factor-α and interleukin (IL)-6, which was accompanied by a reduction in IL-10. Meanwhile, more obvious neuronal and synaptic losses and cognitive impairment were observed. These findings indicate that TREM2 may play a protective role against aging-related neuroinflammation and cognitive impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Tunable denture adhesives using biomimetic principles for enhanced tissue adhesion in moist environments.

    Science.gov (United States)

    Gill, Simrone K; Roohpour, Nima; Topham, Paul D; Tighe, Brian J

    2017-11-01

    Nature provides many interesting examples of adhesive strategies. Of particular note, the protein glue secreted by marine mussels delivers high adhesion in wet and dynamic environments owing to existence of catechol moieties. As such, this study focuses on denture fixatives, where a non-zinc-containing commercial-based formulation has been judiciously modified by a biomimetic catechol-inspired polymer, poly(3,4-dihydroxystyrene/styrene-alt-maleic acid) in a quest to modulate adhesive performance. In vitro studies, in a lap-shear configuration, revealed that the catechol-modified components were able to enhance adhesion to both the denture base and hydrated, functional oral tissue mimic, with the resulting mode of failure prominently being adhesive rather than cohesive. These characteristics are desirable in prosthodontic fixative applications, for which temporary adhesion must be maintained, with ultimately an adhesive failure from the mucosal tissue surface preferred. These insights provide an experimental platform in the design of future biomimetic adhesive systems. Mussel adhesive proteins have proven to be promising biomimetic adhesive candidates for soft tissues and here for the first time we have adapted marine adhesive technology into a denture fixative application. Importantly, we have incorporated a soft tissue mimic in our in vitro adhesion technique that more closely resembles the oral mucosa than previously studied substrates. The novel biomimetic-modified adhesives showed the ability to score the highest adhesive bonding out of all the formulations included in this study, across all moisture levels. This paper will be of major interest to the Acta Biomaterialia readership since the study has illustrated the potential of biomimetic principles in the design of effective prosthodontic tissue adhesives in a series of purpose-designed in vitro experiments in the context of the challenging features of the oral environment. Copyright © 2017 Acta Materialia

  8. [Markers of brain tumors].

    Science.gov (United States)

    Fumagalli, R; Pezzotta, S; Bernini, F; Racagni, G

    1984-05-19

    Biological markers of tumors are compounds or enzymatic activities measurable in body fluids. Their presence or concentration must be linked to tumoral growth. The markers of the central nervous system tumors are detected in CSF. Alpha-feto-protein, carcinoembryonic antigen, human chorionic gonadotropin, adenohypophyseal peptide hormones, enzymes, etc., have found some application in the early diagnosis of leptomeningeal metastasis. Other applications involve the early detection and recurrency of primary brain tumors, as well as the evaluation of efficacy of their therapy. The tests based on the CSF content of desmosterol and polyamines have been studied extensively. Their rationale is discussed and specificity, sensitivity, efficiency and predictive value are considered. Experimental results concerning a new possible biochemical marker, based on CSF concentration of cyclic adenosine monophosphate, are reported.

  9. NP001 regulation of macrophage activation markers in ALS: A phase I clinical and biomarker study

    Science.gov (United States)

    MILLER, ROBERT G.; ZHANG, RONGZHEN; BLOCK, GILBERT; KATZ, JONATHAN; BAROHN, RICHARD; KASARSKIS, EDWARD; FORSHEW, DALLAS; GOPALAKRISHNAN, VIDHYA; MCGRATH, MICHAEL S.

    2017-01-01

    This is a phase I, placebo-controlled, single ascending dose safety and tolerability study of NP001 in patients with ALS. NP001 is a novel regulator of inflammatory macrophages and monocytes. As ALS progression is thought to be related to neuroinflammation, an additional objective of the study was to assess the effects of NP001 administration on monocyte activation markers. Thirty-two ALS patients were enrolled and received either placebo (eight) or one of four (six at each dose) ascending single i.v. doses (0.2, 0.8, 1.6 and 3.2 mg/kg NP001). Patients were monitored for safety, and blood monocyte immune activation markers CD16 and HLA-DR were assessed pre- and 24 h post-dosing. Changes from baseline were calculated. Results showed that NP001 was generally safe and well tolerated. Importantly, a single dose of NP001 caused a dose-dependent reduction in expression of monocyte CD16, a marker of monocyte activation/inflammation. Additionally, monocyte HLA-DR expression was also decreased in those patients with elevated values at baseline. In conclusion, these data indicate that NP001 has an acute effect on inflammatory monocytes in ALS patient blood. The potential for modulation of inflammation in the context of ALS disease progression will require further study with long-term follow-up. PMID:25192333

  10. Tumor Markers: An Overview

    Directory of Open Access Journals (Sweden)

    Ajay G Nayak

    2010-01-01

    Full Text Available Oral cancer is a potentially fatal disease that has been the bane of clinicians throughout the world. Though various modalities of management exist, early detection still provides the best hope for any cancer patient Advances in molecular diagnosis have led to a plethora of choices being available in the fight against cancer. Abnormal cellular products elucidated from malignant cells can be detected and measured in various body tissues and fluids and constitute tumor markers. The various clinical applications and their limitations are covered in the brief overview to help the oral medicine specialist understand the relevant advances made in the field of tumor markers.

  11. Adhesion mechanism of a gecko-inspired oblique structure with an adhesive tip for asymmetric detachment

    Science.gov (United States)

    Sekiguchi, Yu; Takahashi, Kunio; Sato, Chiaki

    2015-12-01

    An adhesion model of an oblique structure with an adhesive tip is proposed by considering a limiting stress for adhesion to describe the detachment mechanism of gecko foot hairs. When a force is applied to the root of the oblique structure, normal and shear stresses are generated at contact and the adhesive tip is detached from the surface when reaching the limiting stress. An adhesion criterion that considers both the normal and shear stresses is introduced, and the asymmetric detachment of the oblique structure is theoretically investigated. In addition, oblique beam array structures are manufactured, and an inclination effect of the structure on the asymmetric detachment is experimentally verified.

  12. Exercise Prevents Enhanced Postoperative Neuroinflammation and Cognitive Decline and Rectifies the Gut Microbiome in a Rat Model of Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Xiaomei Feng

    2017-12-01

    Full Text Available IntroductionPostoperative cognitive decline (PCD can affect in excess of 10% of surgical patients and can be considerably higher with risk factors including advanced age, perioperative infection, and metabolic conditions such as obesity and insulin resistance. To define underlying pathophysiologic processes, we used animal models including a rat model of metabolic syndrome generated by breeding for a trait of low aerobic exercise tolerance. After 35 generations, the low capacity runner (LCR rats differ 10-fold in their aerobic exercise capacity from high capacity runner (HCR rats. The LCR rats respond to surgical procedure with an abnormal phenotype consisting of exaggerated and persistent PCD and failure to resolve neuroinflammation. We determined whether preoperative exercise can rectify the abnormal surgical phenotype.Materials and methodsFollowing institutional approval of the protocol each of male LCR and male HCR rats were randomly assigned to four groups and subjected to isoflurane anesthesia and tibia fracture with internal fixation (surgery or anesthesia alone (sham surgery and to a preoperative exercise regimen that involved walking for 10 km on a treadmill over 6 weeks (exercise or being placed on a stationary treadmill (no exercise. Feces were collected before and after exercise for assessment of gut microbiome. Three days following surgery or sham surgery the rats were tested for ability to recall a contextual aversive stimulus in a trace fear conditioning paradigm. Thereafter some rats were euthanized and the hippocampus harvested for analysis of inflammatory mediators. At 3 months, the remainder of the rats were tested for memory recall by the probe test in a Morris Water Maze.ResultsPostoperatively, LCR rats exhibited exaggerated cognitive decline both at 3 days and at 3 months that was prevented by preoperative exercise. Similarly, LCR rats had excessive postoperative neuroinflammation that was normalized by

  13. Electromagnetic field in control tissue regeneration, pelvic pain, neuro-inflammation and modulation of non-neuronal cells.

    Science.gov (United States)

    Aragona, S E; Mereghetti, G; Lotti, J; Vosa, A; Lotti, T; Canavesi, E

    In scientific literature, magnetic fields are used both in basic science and clinical research. They are often used to treat pain and neuro-inflammation disorders thanks to their influence on cellular responses. Our project was born from the regenerative support that we wanted to give to those diseases characterized by neuro-inflammation, nerve lesion, muscles and tissues disorders that can transform the symptom (e.g. neuropathic pelvic pain) in disease. In this study, we examined the action of pulsed electromagnetic fields (PEMFs) on skin lesion regeneration and the repetitive trans-pelvic magnetic stimulation (rTPMS) on patients affected by incontinence and post-surgical problems, sexual dysfunction, and pelvic pain. In rTPMS for post-surgery urinary incontinence, 40 patients affected by post-surgery urinary incontinence were enrolled. Twenty patients (post-prostatectomy) were treated with rTPMS and 20 with conventional therapies. In PEMF for the regeneration of skin tissue, 50 patients affected by various types of skin lesions (70% low legs vascular lesions) were treated with pulsed electromagnetic fields (PEMFs) twice per week and subsequently with home treatment (Home Care device) twice per day. In rTPMS study, results were evaluated after 3 months. In 10 patients (7 post prostatectomy, 3 cystourethrocele) which were submitted to 18 sessions, twice a week, an improvement of incontinence in 75% of cases with patient compliance was recorded and the quality of life up to 100% also improved. Utilizing PEMFs for the regeneration of skin tissue, following 3 months of AIMED protocol treatment, we reached a reduction of 50% of lesion area in the 60% of cases; 35% of cases healed completely. The use of rTPMS allows training muscles to adequately respond to inflammatory stimulus that causes muscle accommodation deficits with altered contractility or spastic painful contracture in pelvic district. It also stimulates a series of regenerative phenomena due to the action of

  14. Progression of pathology in PINK1-deficient mouse brain from splicing via ubiquitination, ER stress, and mitophagy changes to neuroinflammation.

    Science.gov (United States)

    Torres-Odio, Sylvia; Key, Jana; Hoepken, Hans-Hermann; Canet-Pons, Júlia; Valek, Lucie; Roller, Bastian; Walter, Michael; Morales-Gordo, Blas; Meierhofer, David; Harter, Patrick N; Mittelbronn, Michel; Tegeder, Irmgard; Gispert, Suzana; Auburger, Georg

    2017-08-02

    PINK1 deficiency causes the autosomal recessive PARK6 variant of Parkinson's disease. PINK1 activates ubiquitin by phosphorylation and cooperates with the downstream ubiquitin ligase PARKIN, to exert quality control and control autophagic degradation of mitochondria and of misfolded proteins in all cell types. Global transcriptome profiling of mouse brain and neuron cultures were assessed in protein-protein interaction diagrams and by pathway enrichment algorithms. Validation by quantitative reverse transcriptase polymerase chain reaction and immunoblots was performed, including human neuroblastoma cells and patient primary skin fibroblasts. In a first approach, we documented Pink1-deleted mice across the lifespan regarding brain mRNAs. The expression changes were always subtle, consistently affecting "intracellular membrane-bounded organelles". Significant anomalies involved about 250 factors at age 6 weeks, 1300 at 6 months, and more than 3500 at age 18 months in the cerebellar tissue, including Srsf10, Ube3a, Mapk8, Creb3, and Nfkbia. Initially, mildly significant pathway enrichment for the spliceosome was apparent. Later, highly significant networks of ubiquitin-mediated proteolysis and endoplasmic reticulum protein processing occurred. Finally, an enrichment of neuroinflammation factors appeared, together with profiles of bacterial invasion and MAPK signaling changes-while mitophagy had minor significance. Immunohistochemistry showed pronounced cellular response of Iba1-positive microglia and GFAP-positive astrocytes; brain lipidomics observed increases of ceramides as neuroinflammatory signs at old age. In a second approach, we assessed PINK1 deficiency in the presence of a stressor. Marked dysregulations of microbial defense factors Ifit3 and Rsad2 were consistently observed upon five analyses: (1) Pink1 -/- primary neurons in the first weeks after brain dissociation, (2) aged Pink1 -/- midbrain with transgenic A53T-alpha-synuclein overexpression, (3

  15. Venlafaxine prevents morphine antinociceptive tolerance: The role of neuroinflammation and the l-arginine-nitric oxide pathway.

    Science.gov (United States)

    Mansouri, Mohammad Taghi; Naghizadeh, Bahareh; Ghorbanzadeh, Behnam; Alboghobeish, Soheila; Amirgholami, Neda; Houshmand, Gholamreza; Cauli, Omar

    2018-02-14

    Opioid-induced neuroinflammation and the nitric oxide (NO) signal-transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50 mg/kg) once a day for three consecutive days; the effect of co-administration of VLF (5 or 40 mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l-arginine hydrochloride (l-arg) or NO are involved in the effects rendered by VLF, animals were pre-treated with l-arg (200 mg/kg), or the NO synthesis inhibitors N(ω)-nitro-l-arginine methyl ester (L-NAME; 30 mg/kg) or aminoguanidine hydrochloride (AG; 100 mg/kg), along with VLF (40 mg/kg) for three days before receiving morphine for another three days. Nociception was assessed with a hot-plate test on the fourth day, and the concentration of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-10, brain-derived neurotrophic factor, NO, and oxidative stress factors such as total thiol, malondialdehyde content, and glutathione peroxidase (GPx) activity in the brain was also determined. Co-administration of VLF with morphine attenuated morphine-induced analgesic tolerance and prevented the upregulation of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), NO, and malondialdehyde in brains of mice with induced morphine tolerance; chronic VLF administration inhibited this decrease in brain-derived neurotrophic factor, total thiol, and GPx levels. Moreover, repeated administration of l-arg before receipt of VLF antagonized the effects induced by VLF, while L-NAME and AG potentiated these effects. VLF attenuates morphine-induced analgesic tolerance, at least partly because of its anti

  16. Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation

    Directory of Open Access Journals (Sweden)

    Wu Hsin-Chieh

    2011-04-01

    Full Text Available Abstract Background Apoptosis, neuroinflammation and blood-brain barrier (BBB damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI insults. c-Jun N-terminal kinase (JNK is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups. Methods Overweight (OF pups were established by reducing the litter size to 6, and control (NF pups by keeping the litter size at 12 from postnatal (P day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+ cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose polymerase (PARP, and phospho-JNK and phospho-BimEL levels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK. Results Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+ cells, cleaved levels of caspase-3 and PARP, and ED1-(+ activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+ neurons and RECA1-(+ vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-BimEL levels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in

  17. Krüppel-like factor 4, a novel transcription factor regulates microglial activation and subsequent neuroinflammation

    Directory of Open Access Journals (Sweden)

    Das Sulagna

    2010-10-01

    Full Text Available Abstract Background Activation of microglia, the resident macrophages of the central nervous system (CNS, is the hallmark of neuroinflammation in neurodegenerative diseases and other pathological conditions associated with CNS infection. The activation of microglia is often associated with bystander neuronal death. Nuclear factor-κB (NF-κB is one of the important transcription factors known to be associated with microglial activation which upregulates the expression of inducible nitric oxide synthase (iNOS, cyclooxygenase-2 (Cox-2 and other pro-inflammatory cytokines. Recent studies have focused on the role of Krüppel-like factor 4 (Klf4, one of the zinc-finger transcription factors, in mediating inflammation. However, these studies were limited to peripheral system and its role in CNS is not understood. Our studies focused on the possible role of Klf4 in mediating CNS inflammation. Methods For in vitro studies, mouse microglial BV-2 cell lines were treated with 500 ng/ml Salmonella enterica lipopolysacchride (LPS. Brain tissues were isolated from BALB/c mice administered with 5 mg/kg body weight of LPS. Expressions of Klf4, Cox-2, iNOS and pNF-κB were evaluated using western blotting, quantitative real time PCR, and reverse transcriptase polymerase chain reactions (RT-PCRs. Klf4 knockdown was carried out using SiRNA specific for Klf4 mRNA and luciferase assays and electromobility shift assay (EMSA were performed to study the interaction of Klf4 to iNOS promoter elements in vitro. Co-immunoprecipitation of Klf4 and pNF-κB was done in order to study a possible interaction between the two transcription factors. Results LPS stimulation increased Klf4 expression in microglial cells in a time- and dose-dependent manner. Knockdown of Klf4 resulted in decreased levels of the pro-inflammatory cytokines TNF-α, MCP-1 and IL-6, along with a significant decrease in iNOS and Cox-2 expression. NO production also decreased as a result of Klf4 knockdown

  18. Volume, metabolites and neuroinflammation of the hippocampus in bipolar disorder - A combined magnetic resonance imaging and positron emission tomography study.

    Science.gov (United States)

    Haarman, Bartholomeus C M 'Benno'; Burger, Huibert; Doorduin, Janine; Renken, Remco J; Sibeijn-Kuiper, Anita J; Marsman, Jan-Bernard C; de Vries, Erik F J; de Groot, Jan Cees; Drexhage, Hemmo A; Mendes, Richard; Nolen, Willem A; Riemersma-Van der Lek, Rixt F

    2016-08-01

    The hippocampus is one of the brain regions that is involved in several pathophysiological theories about bipolar disorder (BD), such as the neuroinflammation theory and the corticolimbic metabolic dysregulation theory. We compared hippocampal volume and hippocampal metabolites in bipolar I disorder (BD-I) patients versus healthy controls (HCs) with magnetic resonance imaging (MRI) and spectroscopy (MRS). We post hoc investigated whether hippocampal volume and hippocampal metabolites were associated with microglial activation and explored if potential illness modifying factors affected these hippocampal measurements and whether these were associated with experienced mood and functioning. Twenty-two BD-I patients and twenty-four HCs were included in the analyses. All subjects underwent psychiatric interviews as well as an MRI scan, including a T1 scan and PRESS magnetic resonance spectroscopy (MRS). Volumetric analysis was performed with Freesurfer. MRS quantification was performed with LC Model. A subgroup of 14 patients and 11 HCs also underwent a successful [(11)C]-(R)-PK11195 neuroinflammation positron emission tomography scan. In contrast to our hypothesis, hippocampal volumes were not decreased in patients compared to HC after correcting for individual whole-brain volume variations. We demonstrated decreased N-acetylaspartate (NAA)+N-acetyl-aspartyl-glutamate (NAAG) and creatine (Cr)+phosphocreatine (PCr) concentrations in the left hippocampus. In the explorative analyses in the left hippocampus we identified positive associations between microglial activation and the NAA+NAAG concentration, between alcohol use and NAA+NAAG concentration, between microglial activation and the depression score and a negative relation between Cr+PCr concentration and experienced occupational disability. Duration of illness associated positively with volume bilaterally. Compared to HCs, the decreased NAA+NAAG concentration in the left hippocampus of BD-I patients suggests a

  19. Tuneable adhesion through novel binder technologies

    NARCIS (Netherlands)

    Wouters, M.E.L.; Burghoorn, M.M.A.; Ingenhut, B.; Timmer, K.; Rentrop, C.H.A.; Bots, T.L.; Oosterhuis, G.; Fischer, H.R.

    2011-01-01

    A reversible crosslinking mechanism enabling bonding and debonding of adhesives and coatings based on Diels-Alder chemistry is described. The Diels-Alder compounds form a covalently crosslinked network at low temperatures that break at elevated temperatures. As a result, the adhesive exhibits good

  20. Enzymatically degradable mussel-inspired adhesive hydrogel.

    Science.gov (United States)

    Brubaker, Carrie E; Messersmith, Phillip B

    2011-12-12

    Mussel-inspired adhesive hydrogels represent innovative candidate medical sealants or glues. In the present work, we describe an enzyme-degradable mussel-inspired adhesive hydrogel formulation, achieved by incorporating minimal elastase substrate peptide Ala-Ala into the branched poly(ethylene glycol) (PEG) macromonomer structure. The system takes advantage of neutrophil elastase expression upregulation and secretion from neutrophils upon recruitment to wounded or inflamed tissue. By integrating adhesive degradation behaviors that respond to cellular cues, we expand the functional range of our mussel-inspired adhesive hydrogel platforms. Rapid (adhesion of the proteolytically active, catechol-terminated precursor macromonomer was achieved by addition of sodium periodate oxidant. Rheological analysis and equilibrium swelling studies demonstrated that the hydrogel is appropriate for soft tissue-contacting applications. Notably, hydrogel storage modulus (G') achieved values on the order of 10 kPa, and strain at failure exceeded 200% strain. Lap shear testing confirmed the material's adhesive behavior (shear strength: 30.4 ± 3.39 kPa). Although adhesive hydrogel degradation was not observed during short-term (27 h) in vitro treatment with neutrophil elastase, in vivo degradation proceeded over several months following dorsal subcutaneous implantation in mice. This work represents the first example of an enzymatically degradable mussel-inspired adhesive and expands the potential biomedical applications of this family of materials.

  1. CHARACTERIZATION OF ULTRASONIC ASSISTED ADHESIVE JOINTS

    Directory of Open Access Journals (Sweden)

    Rainer Pauska

    2016-02-01

    Full Text Available Joining experiments using different adhesives were carried out. In addition to the adhesive, the specimens were also treated with ultrasonic waves to improve the load carrying capacity of the joined parts. Lap joint shear tests have been conducted to quantify this improvement.

  2. Adhesive arachnoiditis in patients with spinal block

    Energy Technology Data Exchange (ETDEWEB)

    Skalpe, I.O.; Sortland, O.

    1982-01-01

    Adhesive arachnoiditis was found in eight patients and spinal block was found in 7 of these in a series of 330 patients refered for thoracic myelography. This variety of adhesive arachnoiditis seems to be caused by spinal block/high CSF protein concentration.

  3. Recurrent spinal adhesive arachnoiditis: a case report

    Directory of Open Access Journals (Sweden)

    James Pitágoras de Mattos

    1988-03-01

    Full Text Available Spinal adhesive arachnoiditis is not an uncommon disease, usually having a monophasic course. We studied an atypical patient with recurrent spinal adhesive arachnoiditis nine years after intrathecal anesthesia and the first attack of the disease. Also noteworthy was the favorable evolution after surgery.

  4. Degradable Adhesives for Surgery and Tissue Engineering.

    Science.gov (United States)

    Bhagat, Vrushali; Becker, Matthew L

    2017-10-09

    This review highlights the research on degradable polymeric tissue adhesives for surgery and tissue engineering. Included are a comprehensive listing of specific uses, advantages, and disadvantages of different adhesive groups. A critical evaluation of challenges affecting the development of next generation materials is also discussed, and insights into the outlook of the field are explored.

  5. Influence of Blood Contamination During Multimode Adhesive ...

    African Journals Online (AJOL)

    2018-01-30

    Jan 30, 2018 ... decontamination method prevented the decrease in µTBS when contamination occurred after light curing. Drying the blood contaminants and reapplying the adhesive may regain the dentin adhesion when contamination occurs before light curing. Alternatively, rinsing and drying contaminants followed by ...

  6. Biobased adhesives and non-conventional bonding

    Science.gov (United States)

    Charles Frihart

    2010-01-01

    Biobased adhesives fall into several major classes based upon their chemical structures. Starches are used in large volume, especially in the paper products industries, but cellulosics generally do not have the strength and water resistance needed for most wood products. Several authors have covered cellulosics adhesives (Baumann and Conner 2002, Pizzi 2006). However...

  7. Age Increases Monocyte Adhesion on Collagen

    Science.gov (United States)

    Khalaji, Samira; Zondler, Lisa; Kleinjan, Fenneke; Nolte, Ulla; Mulaw, Medhanie A.; Danzer, Karin M.; Weishaupt, Jochen H.; Gottschalk, Kay-E.

    2017-05-01

    Adhesion of monocytes to micro-injuries on arterial walls is an important early step in the occurrence and development of degenerative atherosclerotic lesions. At these injuries, collagen is exposed to the blood stream. We are interested whether age influences monocyte adhesion to collagen under flow, and hence influences the susceptibility to arteriosclerotic lesions. Therefore, we studied adhesion and rolling of human peripheral blood monocytes from old and young individuals on collagen type I coated surface under shear flow. We find that firm adhesion of monocytes to collagen type I is elevated in old individuals. Pre-stimulation by lipopolysaccharide increases the firm adhesion of monocytes homogeneously in older individuals, but heterogeneously in young individuals. Blocking integrin αx showed that adhesion of monocytes to collagen type I is specific to the main collagen binding integrin αxβ2. Surprisingly, we find no significant age-dependent difference in gene expression of integrin αx or integrin β2. However, if all integrins are activated from the outside, no differences exist between the age groups. Altered integrin activation therefore causes the increased adhesion. Our results show that the basal increase in integrin activation in monocytes from old individuals increases monocyte adhesion to collagen and therefore the risk for arteriosclerotic plaques.

  8. Syndecans: synergistic activators of cell adhesion

    DEFF Research Database (Denmark)

    Woods, A; Couchman, J R

    1998-01-01

    Cell-surface proteoglycans participate in cell adhesion, growth-factor signalling, lipase activity and anticoagulation. Until recently, only the roles of the glycosaminoglycan chains were investigated. Now, with molecular characterization of several core proteins, the roles of each individual...... molecules modulating integrin-based adhesion....

  9. Scaling Principles for Understanding and Exploiting Adhesion

    Science.gov (United States)

    Crosby, Alfred

    A grand challenge in the science of adhesion is the development of a general design paradigm for adhesive materials that can sustain large forces across an interface yet be detached with minimal force upon command. Essential to this challenge is the generality of achieving this performance under a wide set of external conditions and across an extensive range of forces. Nature has provided some guidance through various examples, e.g. geckos, for how to meet this challenge; however, a single solution is not evident upon initial investigation. To help provide insight into nature's ability to scale reversible adhesion and adapt to different external constraints, we have developed a general scaling theory that describes the force capacity of an adhesive interface in the context of biological locomotion. We have demonstrated that this scaling theory can be used to understand the relative performance of a wide range of organisms, including numerous gecko species and insects, as well as an extensive library of synthetic adhesive materials. We will present the development and testing of this scaling theory, and how this understanding has helped guide the development of new composite materials for high capacity adhesives. We will also demonstrate how this scaling theory has led to the development of new strategies for transfer printing and adhesive applications in manufacturing processes. Overall, the developed scaling principles provide a framework for guiding the design of adhesives.

  10. Mechanisms of temporary adhesion in benthic animals

    NARCIS (Netherlands)

    Dodou, D.; Breedveld, P.; Winter, J.C.F.; Dankelman, J.; Leeuwen, van J.L.

    2011-01-01

    Adhesive systems are ubiquitous in benthic animals and play a key role in diverse functions such as locomotion, food capture, mating, burrow building, and defence. For benthic animals that release adhesives, surface and material properties and external morphology have received little attention

  11. Is nonoperative management of adhesive intestinal obstruction ...

    African Journals Online (AJOL)

    Background: Nonoperative management of adhesive intestinal obstruction gives good results in adults but there are scant studies on its outcome in children. This study reports outcomes and experiences with nonoperative and operative management of adhesive intestinal obstruction in children in a resource-poor country.

  12. Influence of Blood Contamination During Multimode Adhesive ...

    African Journals Online (AJOL)

    Objectives: The present study evaluated the effects of blood contamination performed at different steps of bonding on the microtensile bond strength (μTBS) of multimode adhesives to dentin when using the self-etch approach. Materials and Methods: Seventy-five molars were randomly assigned to three adhesive groups ...

  13. Film adhesion in amorphous silicon solar cells

    Indian Academy of Sciences (India)

    A major issue encountered during fabrication of triple junction -Si solar cells on polyimide substrates is the adhesion of the solar cell thin films to the substrates. Here, we present our study of film adhesion in amorphous silicon solar cells made on different polyimide substrates (Kapton VN, Upilex-S and Gouldflex), and the ...

  14. Chapter 16: Soy Proteins as Wood Adhesives

    Science.gov (United States)

    Charles R. Frihart; Christopher G. Hunt; Michael J. Birkeland

    2014-01-01

    Protein adhesives allowed the development of bonded wood products such as plywood and glulam in the early 20th century. Petrochemical-based adhesives replaced proteins in most wood bonding applications because of lower cost, improved production efficiencies, and enhanced durability. However, several technological and environmental factors have led to a resurgence of...

  15. Film adhesion in amorphous silicon solar cells

    Indian Academy of Sciences (India)

    TECS

    Abstract. A major issue encountered during fabrication of triple junction a-Si solar cells on polyimide sub- strates is the adhesion of the solar cell thin films to the substrates. Here, we present our study of film adhesion in amorphous silicon solar cells made on different polyimide substrates (Kapton VN, Upilex-S and ...

  16. Predicting Failure Initiation in Structural Adhesive Joints

    Science.gov (United States)

    2012-08-15

    Elastoplástico de Adhesivos – Modeling, characterization and simulation of the elastoplastic behavior of adhesives. Maestría en Ciencia de Materiales...adhesive and a 1018 steel”. Maestría en Ciencia de Materiales. Centro de Investigación en Materiales Avanzados S.C. May 2012.  Abstract: In the

  17. Adhesion of Zinc Hot-dip Coatings

    Directory of Open Access Journals (Sweden)

    Michal Černý

    2014-01-01

    Full Text Available The work is focused on verification of quality adhesion of zinc coating. It describes elements which affect quality and adhesive solidity within the coating. For assessment itself it will be neccessary to get know the basic elements which can affect adhesion of hot-dip coating which will be essential for choosing suitable samples for verification itself. These elements characterise acoustic responses during delamination coating. They affect elements influencing progress of signal. In research there is also a summary of existing methods for testing adhesion of coatings. As a result a new proposal of a new method comes out for purpose of quality testing of adhesion zinc hot-dip coating. The results of verification of this method are put to scientific analysis and findings lead to assessment of proposed method and its application in technical practise.The goal of this contribution is also include to proposed methodology testing adhesion zinc coating by nondestructive diagnostic method of acoustic emission (AE, which would monitor characterise progress of coating delamination of hot-dip zinc from basic material in way to adhesion tests would be practicable in situ. It can be enabled by analysis and assessment of results acquired by method AE and its application within verification of new method of adhesion anti-corrosive zinc coating.

  18. Wood structure and adhesive bond strength

    Science.gov (United States)

    Charles R. Frihart

    2006-01-01

    Much of the literature on the bonding of wood and other lignocellulosic materials has concentrated on traditional adhesion theories. This has led to misconceptions because wood is a porous material on both the macroscopic and microscopic levels. A better understanding of wood bonding can be developed by investigating the theories of adhesion and bond strength, taking...

  19. Electrostatic adhesion testing of electronic metallizations

    Science.gov (United States)

    Yang, H. S.; Brotzen, F. R.; Callahan, D. L.; Dunn, C. F.

    1997-06-01

    A novel technique is developed to measure quantitatively the adhesion strength of metallizations deposited on substrates such as silicon. Electrostatic adhesion testing employs electrostatic forces to generate delaminating stresses in thin metallic films. The interfacial adhesion strength is readily calculated from the electrode geometry and the applied electrostatic field at failure. Unlike other adhesion tests, this technique does not require any mechanical contact and is virtually independent of the plastic deformation of the film. Furthermore, this test provides direct strength measurements as opposed to work or energy of adhesion measurements obtained by the common peel test. The adhesion strengths of several metallizations (Cu, Al) are characterized using the electrostatic technique. The distribution of stress-at-failure data follows Weibull failure statistics. Field emission scanning electron microscopy reveals that the films are delaminated in a microblister-type mode. It is shown that electrostatic adhesion testing is effective in providing quantitative values for the adhesion strengths and failure probabilities of thin-film metallizations.

  20. Beneficial effects of lycopene against haloperidol induced orofacial dyskinesia in rats: Possible neurotransmitters and neuroinflammation modulation.

    Science.gov (United States)

    Datta, Swati; Jamwal, Sumit; Deshmukh, Rahul; Kumar, Puneet

    2016-01-15

    Tardive Dyskinesia is a severe side effect of chronic neuroleptic treatment consisting of abnormal involuntary movements, characterized by orofacial dyskinesia. The study was designed to investigate the protective effect of lycopene against haloperidol induced orofacial dyskinesia possibly by neurochemical and neuroinflammatory modulation in rats. Rats were administered with haloperidol (1mg/kg, i.p for 21 days) to induce orofacial dyskinesia. Lycopene (5 and 10mg/kg, p.o) was given daily 1hour before haloperidol treatment for 21 days. Behavioral observations (vacuous chewing movements, tongue protrusions, facial jerking, rotarod activity, grip strength, narrow beam walking) were assessed on 0th, 7th(,) 14th(,) 21st day after haloperidol treatment. On 22nd day, animals were killed and striatum was excised for estimation of biochemical parameters (malondialdehyde, nitrite and endogenous enzyme (GSH), pro-inflammatory cytokines [Tumor necrosis factor, Interleukin 1β, Interleukin 6] and neurotransmitters level (dopamine, serotonin, nor epinephrine, 5-Hydroxyindole acetic acid (5-HIAA), Homovanillic acid, 3,4- dihydroxyphenylacetic acid. Haloperidol treatment for 21 days impaired muscle co-ordination, motor activity and grip strength with an increased in orofacial dyskinetic movements. Further free radical generation increases MDA and nitrite levels, decreasing GSH levels in striatum. Neuroinflammatory markers were significantly increased with decrease in neurotransmitters levels. Lycopene (5 and 10mg/kg, p.o) treatment along with haloperidol significantly attenuated impairment in behavioral, biochemical, neurochemical and neuroinflammatory markers. Results of the present study attributed the therapeutic potential of lycopene in the treatment (prevented or delayed) of typical antipsychotic induced orofacial dyskinesia. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Genetics Home Reference: leukocyte adhesion deficiency type 1

    Science.gov (United States)

    ... Health Conditions Leukocyte adhesion deficiency type 1 Leukocyte adhesion deficiency type 1 Printable PDF Open All Close ... to view the expand/collapse boxes. Description Leukocyte adhesion deficiency type 1 is a disorder that causes ...

  2. Interpenetrating Polymer Network (IPN) Adhesives for Electron Beam Cure

    National Research Council Canada - National Science Library

    Sands, James

    2000-01-01

    Electron beam (e-beam)-processed polymer adhesives have historically performed poorly compared to traditional adhesive technologies due to a lack of toughness engineered into these new types of adhesive materials...

  3. Carbon nanotube dry adhesives with temperature-enhanced adhesion over a large temperature range

    Science.gov (United States)

    Xu, Ming; Du, Feng; Ganguli, Sabyasachi; Roy, Ajit; Dai, Liming

    2016-11-01

    Conventional adhesives show a decrease in the adhesion force with increasing temperature due to thermally induced viscoelastic thinning and/or structural decomposition. Here, we report the counter-intuitive behaviour of carbon nanotube (CNT) dry adhesives that show a temperature-enhanced adhesion strength by over six-fold up to 143 N cm-2 (4 mm × 4 mm), among the strongest pure CNT dry adhesives, over a temperature range from -196 to 1,000 °C. This unusual adhesion behaviour leads to temperature-enhanced electrical and thermal transports, enabling the CNT dry adhesive for efficient electrical and thermal management when being used as a conductive double-sided sticky tape. With its intrinsic thermal stability, our CNT adhesive sustains many temperature transition cycles over a wide operation temperature range. We discover that a `nano-interlock' adhesion mechanism is responsible for the adhesion behaviour, which could be applied to the development of various dry CNT adhesives with novel features.

  4. Evaluation of Advanced Adhesives for Aerospace Structures

    Science.gov (United States)

    Stoyanov, P.; Rodriguez, N.; Dickinson, T.; Huy Nguyen, D.; Park, E.; Foyos, J.; Hernandez, V.; Ogren, J.; Berg, M.; Es-Said, O. S.

    2008-08-01

    Polymer adhesives are finding increased use in panel joining applications in aircraft and aerospace structures where the applied stresses permit their use and where a uniform stress distribution is needed. One such adhesive, Hysol EA-9394™, was compared to three other formulations in this study. The new formulations were Hysol EA-9396, Hysol EA-9396 filled with nickel nanofibers and mixed by machine (Jamesbury Blender), and Hysol EA-9396 filled with nickel nanofibers and hand mixed in the laboratory. The comparison consisted of measuring shear lap strengths of aluminum test pieces bonded together with the candidate adhesives. The mechanical tests were supplemented by a Weibull analysis of the strength data and by a visual inspection of the failure mode (adhesive/cohesive). The lap shear strengths (fracture stress values) of all three Hysol EA-9396 adhesives were greater than that of the baseline Hysol EA-9394 polymer.

  5. Ratcheting in a nonlinear viscoelastic adhesive

    Science.gov (United States)

    Lemme, David; Smith, Lloyd

    2017-11-01

    Uniaxial time-dependent creep and cycled stress behavior of a standard and toughened film adhesive were studied experimentally. Both adhesives exhibited progressive accumulation of strain from an applied cycled stress. Creep tests were fit to a viscoelastic power law model at three different applied stresses which showed nonlinear response in both adhesives. A third order nonlinear power law model with a permanent strain component was used to describe the creep behavior of both adhesives and to predict creep recovery and the accumulation of strain due to cycled stress. Permanent strain was observed at high stress but only up to 3% of the maximum strain. Creep recovery was under predicted by the nonlinear model, while cycled stress showed less than 3% difference for the first cycle but then over predicted the response above 1000 cycles by 4-14% at high stress. The results demonstrate the complex response observed with structural adhesives, and the need for further analytical advancements to describe their behavior.

  6. Cyanoacrylate adhesive technique in wound edge approximation.

    Science.gov (United States)

    Prahlow, J A; Lantz, P E

    1993-11-01

    Cyanoacrylate, the adhesive component of many commercially available strong-binding glues, has been used by the medical profession for various purposes, including tissue adhesion and repair, embolization, sclerotherapy, and hemostasis. Mortuary science professionals rely on cyanoacrylate's adhesive property to aid in body restoration techniques following embalming. Forensic applications include the use of cyanoacrylate fumes for latent fingerprint detection. An additional application for this sticky chemical is currently unrecognized by many within the forensic community. Specifically, cyanoacrylate's adhesive property makes possible the relatively simple, efficient, and rapid approximation of disrupted skin and tissue when warranted during a forensic autopsy. The final result is aesthetically pleasing and lends itself to subsequent photographic documentation especially when patterned injuries are encountered. We discuss the technique, benefits, and limitations of the cyanoacrylate adhesive method in this setting and present several cases wherein the technique has produced satisfying results.

  7. Viscosity and adhesion strength of cream-type denture adhesives and mouth moisturizers.

    Science.gov (United States)

    Kano, Hiroshi; Kurogi, Tadafumi; Shimizu, Takaharu; Nishimura, Masahiro; Murata, Hiroshi

    2012-01-01

    We evaluated adhesion strength to acrylic resins under various experimental conditions and viscosity of 4 cream-type denture adhesives and 2 mouth moisturizers. The viscosity was determined by a sine-wave vibro viscometer. The adhesion strength tests were performed with 2 resin plates at a universal tester. In Method A, various constant thicknesses of material layer were tested and tensile strength was measured, while in Method B a constant load was applied before measurement. Five tests were carried out for each measurement. With Method A, adhesion strength increased exponentially as the layer got thin. Effect of the material thicknesses (contribution ratio ρ=79.0%) was much larger than that of material type (ρ=15.3%). Materials with higher viscosity had greater levels of adhesion strength in Method A, whereas those with the higher viscosity had lower levels of adhesion strength in Method B. Adhesion strength was significantly affected by the experimental condition prior to applying tension.

  8. Adhesives for orthodontic bracket bonding

    Directory of Open Access Journals (Sweden)

    Déborah Daniella Diniz Fonseca

    2010-04-01

    Full Text Available The advent of acid etching, introduced by Buonocore in 1955, brought the possibility of bonding between the bracket base and enamel, contributing to more esthetic and conservative orthodontics. This direct bracket bonding technique has brought benefits such as reduced cost and time in performing the treatment, as well as making it easier to perform oral hygiene. The aim of this study was to conduct a survey of published studies on orthodontic bracket bonding to dental enamel. It was verified that resin composites and glass ionomer are the most studied and researched materials for this purpose. Resin-modified glass ionomer, with its biocompatibility, capacity of releasing fluoride and no need for acid etching on the tooth structure, has become increasingly popular among dentists. However, due to the esthetic and mechanical properties of light polymerizable resin composite, it continues to be one of the adhesives of choice in the bracket bonding technique and its use is widely disseminated.

  9. Multibody simulation of adhesion pili

    CERN Document Server

    Zakrisson, Johan; Servin, Martin; Axner, Ove; Lacoursiere, Claude; Andersson, Magnus

    2014-01-01

    We present a coarse grained rigid multibody model of a subunit assembled helix-like polymer, e.g., adhesion pili expressed by bacteria, that is capable of describing the polymers force-extension response. With building blocks representing individual subunits the model appropriately describes the complex behavior of pili expressed by the gram-negative uropathogenic Escherichia coli bacteria under the action of an external force. Numerical simulations show that the dynamics of the model, which include both the effects of unwinding and rewinding, are in good quantitative agreement with the characteristic force-extension response as observed experimentally for type 1 and P pili. By tuning the model, it is also possible to reproduce the force-extension response in the presence of anti-shaft antibodies, which dramatically changes the mechanical properties. Thus, the model and the results in this work give enhanced understanding of how a pilus unwinds under action of external forces and provide new perspective of th...

  10. Post-exposure administration of diazepam combined with soluble epoxide hydrolase inhibition stops seizures and modulates neuroinflammation in a murine model of acute TETS intoxication

    Energy Technology Data Exchange (ETDEWEB)

    Vito, Stephen T., E-mail: stvito@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Austin, Adam T., E-mail: aaustin@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Banks, Christopher N., E-mail: Christopher.Banks@oehha.ca.gov [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Inceoglu, Bora, E-mail: abinceoglu@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Bruun, Donald A., E-mail: dabruun@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States); Zolkowska, Dorota, E-mail: dzolkowska@gmail.com [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Tancredi, Daniel J., E-mail: djtancredi@ucdavis.edu [Department of Pediatrics, School of Medicine, University of California-Davis Medical Center, Sacramento, CA 95817 (United States); Rogawski, Michael A., E-mail: rogawski@ucdavis.edu [Department of Neurology, School of Medicine, University of California-Davis, Sacramento, CA 95817 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology, College of Agricultural and Environmental Sciences, University of California-Davis, Davis, CA 95616 (United States); Lein, Pamela J., E-mail: pjlein@ucdavis.edu [Department of Molecular Biosciences, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616 (United States)

    2014-12-01

    Tetramethylenedisulfotetramine (TETS) is a potent convulsant poison for which there is currently no approved antidote. The convulsant action of TETS is thought to be mediated by inhibition of type A gamma-aminobutyric acid receptor (GABA{sub A}R) function. We, therefore, investigated the effects of post-exposure administration of diazepam, a GABA{sub A}R positive allosteric modulator, on seizure activity, death and neuroinflammation in adult male Swiss mice injected with a lethal dose of TETS (0.15 mg/kg, ip). Administration of a high dose of diazepam (5 mg/kg, ip) immediately following the second clonic seizure (approximately 20 min post-TETS injection) effectively prevented progression to tonic seizures and death. However, this treatment did not prevent persistent reactive astrogliosis and microglial activation, as determined by GFAP and Iba-1 immunoreactivity and microglial cell morphology. Inhibition of soluble epoxide hydrolase (sEH) has been shown to exert potent anti-inflammatory effects and to increase survival in mice intoxicated with other GABA{sub A}R antagonists. The sEH inhibitor TUPS (1 mg/kg, ip) administered immediately after the second clonic seizure did not protect TETS-intoxicated animals from tonic seizures or death. Combined administration of diazepam (5 mg/kg, ip) and TUPS (1 mg/kg, ip, starting 1 h after diazepam and repeated every 24 h) prevented TETS-induced lethality and influenced signs of neuroinflammation in some brain regions. Significantly decreased microglial activation and enhanced reactive astrogliosis were observed in the hippocampus, with no changes in the cortex. Combining an agent that targets specific anti-inflammatory mechanisms with a traditional antiseizure drug may enhance treatment outcome in TETS intoxication. - Highlights: • Acute TETS intoxication causes delayed and persistent neuroinflammation. • Diazepam given post-TETS prevents lethal tonic seizures but not neuroinflammation. • A soluble epoxide hydrolase

  11. Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation, oxidative stress, and brain injury in mice with ischemic stroke and bone fracture.

    Science.gov (United States)

    Han, Zhenying; Li, Li; Wang, Liang; Degos, Vincent; Maze, Mervyn; Su, Hua

    2014-11-01

    Bone fracture at the acute stage of stroke exacerbates stroke injury by increasing neuroinflammation. We hypothesize that activation of α-7 nicotinic acetylcholine receptor (α-7 nAchR) attenuates neuroinflammation and oxidative stress, and reduces brain injury in mice with bone fracture and stroke. Permanent middle cerebral artery occlusion (pMCAO) was performed in C57BL/6J mice followed by tibia fracture 1 day later. Mice were treated with 0.8 mg/kg PHA 568487 (PHA, α-7 nAchR-specific agonist), 6 mg/kg methyllycaconitine (α-7 nAchR antagonist), or saline 1 and 2 days after pMCAO. Behavior was tested 3 days after pMCAO. Neuronal injury, CD68(+) , M1 (pro-inflammatory) and M2 (anti-inflammatory) microglia/macrophages, phosphorylated p65 component of nuclear factor kappa b in microglia/macrophages, oxidative and anti-oxidant gene expression were quantified. Compared to saline-treated mice, PHA-treated mice performed better in behavioral tests, had fewer apoptotic neurons (NeuN(+) TUNEL(+) ), fewer CD68(+) and M1 macrophages, and more M2 macrophages. PHA increased anti-oxidant gene expression and decreased oxidative stress and phosphorylation of nuclear factor kappa b p65. Methyllycaconitine had the opposite effects. Our data indicate that α-7 nAchR agonist treatment reduces neuroinflammation and oxidative stress, which are associated with reduced brain injury in mice with ischemic stroke plus tibia fracture. Bone fracture at the acute stage of stroke exacerbates neuroinflammation, oxidative stress, and brain injury, and our study has shown that the α-7 nAchR agonist, PHA (PHA 568487), attenuates neuroinflammation, oxidative stress, and brain injury in mice with stroke and bone fracture. Hence, PHA could provide an opportunity to develop a new strategy to reduce brain injury in patients suffering from stroke and bone fracture. © 2014 International Society for Neurochemistry.

  12. Cell adhesion and apoptosis in ovarian stromal hyperplasia and hyperthecosis.

    Science.gov (United States)

    Sharabidze, N; Burkadze, G; Sabakhtarashvili, M

    2006-02-01

    The aim of our study was to investigate cell adhesion and apoptosis in ovarian stromal hyperplasia and hyperthecosis in reproductive women with and without polycystic ovarian disease. We have studied 104 patients with a histological diagnosis of ovarian stromal hyperthecosis and stromal hyperplasia. Paraffin sections were stained by hematoxylin-eosin, von Gieson and immunohistochemistry for Bcl-2 (anti-apoptotic protein) and E-cadherin (cell adhesion marker). We assessed the number of Bcl-2-positive and E-cadherin-positive cells. The patients were divided into 4 groups: group 1-33 patients with polycystic ovarian disease and coexistent stromal hyperthecosis, group 2-28 patients with polycystic ovarian disease and coexistent stromal hyperplasia, group 3-24 patients with ovarian stromal hyperthecosis, group 4-19 patients with ovarian stromal hyperplasia. Our results suggest that in ovarian stromal hyperthecosis and stromal hyperplasia coexistent with polycystic ovarian disease, E-cadherin-positivity in internal and external theca cells, and granulosa cells is associated with Bcl-2 expression. Therefore, ovarian cells expressing Bcl-2 and maintaining E-cadherin-positivity may be the viable cells that escape the apoptotic process. In ovarian stromal hyperthecosis without polycystic ovarian disease, luteinized stromal cells are potentially resistant to apoptosis as they are positive for Bcl-2. In ovarian stromal hyperplasia without polycystic ovarian disease, hyperplastic stromal cells are potentially susceptible to apoptosis as they are negative for Bcl-2. E-cadherin is negative both in stromal hyperthecosis and hyperplasia suggesting that E-cadherin expression in ovary is limited to granulosa and theca cells only. Described characteristics of cell adhesion and apoptosis may play a role in pathogenesis of ovarian stromal hyperthecosis and stromal hyperplasia with and without polycystic ovarian disease.

  13. Magik Markers Trehvis

    Index Scriptorium Estoniae

    2008-01-01

    Müra-rock'i viljelevast USA duost Magik Markers (ansambel osaleb režissöör Veiko Õunapuu uue mängufilmi "Püha Tõnu kiusamine" võtetel, kontsert 15. nov. Tartus klubis Trehv, vt. www.magikmarkers.audiosport.org.)

  14. (DArT) markers

    Indian Academy of Sciences (India)

    2EH Graham Centre for Agricultural Innovation (NSW Department of Industry and Investment and Charles Sturt. University), P. O. Box 588 Wagga Wagga, .... between-cluster variance in relative hybridization intensity as a percentage of the total .... markers tend to cluster on one or two linkage groups. The data of both sets of ...

  15. The Swift Turbidity Marker

    Science.gov (United States)

    Omar, Ahmad Fairuz; MatJafri, Mohd Zubir

    2011-01-01

    The Swift Turbidity Marker is an optical instrument developed to measure the level of water turbidity. The components and configuration selected for the system are based on common turbidity meter design concepts but use a simplified methodology to produce rapid turbidity measurements. This work is aimed at high school physics students and is the…

  16. Writing on water with permanent markers

    Science.gov (United States)

    Khodaparast, Sepideh; Boulogne, François; Stone, Howard A.

    2016-11-01

    Permanent markers create a continuous thin stain on a surface, which, after drying, can only be removed by high pressure cleaning or organic solvents. The stains of the markers are hydrophobic and thus effectively resist rinsing by water. We introduce a peeling technique based on surface tension, which benefits from this hydrophobicity, to transfer complex two-dimensional marks onto the air-water interface. As an air-water meniscus reaches the stain edge, the surface tension applies a detachment force to the thin layer. If larger than the adhesion of the stain on the substrate, the surface tension can peel off the entire layer. We examine the efficiency of this peeling method for elastic thin films in an experimental model made of thin polystyrene films of well-controlled geometrical properties adhering on clean glass substrates. We investigate the effect of film thickness and interface velocity. At low interface velocities U cleaning the water proof stains without solvent and fabrication of flexible wearable electronics. This research is supported by Grant from Swiss National Science Foundation (P2ELP2-158896).

  17. Tissue adhesives for closure of surgical incisions.

    Science.gov (United States)

    Dumville, Jo C; Coulthard, Paul; Worthington, Helen V; Riley, Philip; Patel, Neil; Darcey, James; Esposito, Marco; van der Elst, Maarten; van Waes, Oscar J F

    2014-11-28

    Sutures (stitches), staples and adhesive tapes have been used for many years as methods of wound closure, but tissue adhesives have entered clinical practice more recently. Closure of wounds with sutures enables the closure to be meticulous, but the sutures may show tissue reactivity and can require removal. Tissue adhesives offer the advantages of an absence of risk of needlestick injury and no requirement to remove sutures later. Initially, tissue adhesives were used primarily in emergency room settings, but this review looks at the use of tissue adhesives in the operating room/theatre where surgeons are using them increasingly for the closure of surgical skin incisions. To determine the effects of various tissue adhesives compared with conventional skin closure techniques for the closure of surgical wounds. In March 2014 for this second update we searched the Cochrane Wounds Group Specialised Register; The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE and EBSCO CINAHL. We did not restrict the search and study selection with respect to language, date of publication or study setting. Only randomised controlled trials were eligible for inclusion. We conducted screening of eligible studies, data extraction and risk of bias assessment independently and in duplicate. We expressed results as random-effects models using mean difference for continuous outcomes and risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. We investigated heterogeneity, including both clinical and methodological factors. This second update of the review identified 19 additional eligible trials resulting in a total of 33 studies (2793 participants) that met the inclusion criteria. There was low quality evidence that sutures were significantly better than tissue adhesives for reducing the risk of wound breakdown (dehiscence; RR 3.35; 95% CI 1.53 to 7

  18. Adhesion protein protocols [Methods in molecular biology, v. 96

    National Research Council Canada - National Science Library

    Dejana, Elisabetta; Corada, Monica

    1999-01-01

    "An international corps of expert investigators describe their optimized techniques for both the identification of new cell adhesion proteins and for the characterization of novel adhesive structures...

  19. Adhesion Molecules Associated with Female Genital Tract Infection.

    Directory of Open Access Journals (Sweden)

    Jamal Qualai

    Full Text Available Efforts to develop vaccines that can elicit mucosal immune responses in the female genital tract against sexually transmitted infections have been hampered by an inability to measure immune responses in these tissues. The differential expression of adhesion molecules is known to confer site-dependent homing of circulating effector T cells to mucosal tissues. Specific homing molecules have been defined that can be measured in blood as surrogate markers of local immunity (e.g. α4β7 for gut. Here we analyzed the expression pattern of adhesion molecules by circulating effector T cells following mucosal infection of the female genital tract in mice and during a symptomatic episode of vaginosis in women. While CCR2, CCR5, CXCR6 and CD11c were preferentially expressed in a mouse model of Chlamydia infection, only CCR5 and CD11c were clearly expressed by effector T cells during bacterial vaginosis in women. Other homing molecules previously suggested as required for homing to the genital mucosa such as α4β1 and α4β7 were also differentially expressed in these patients. However, CD11c expression, an integrin chain rarely analyzed in the context of T cell immunity, was the most consistently elevated in all activated effector CD8+ T cell subsets analyzed. This molecule was also induced after systemic infection in mice, suggesting that CD11c is not exclusive of genital tract infection. Still, its increase in response to genital tract disorders may represent a novel surrogate marker of mucosal immunity in women, and warrants further exploration for diagnostic and therapeutic purposes.

  20. Peritoneal adhesions after laparoscopic gastrointestinal surgery.

    Science.gov (United States)

    Mais, Valerio

    2014-05-07

    Although laparoscopy has the potential to reduce peritoneal trauma and post-operative peritoneal adhesion formation, only one randomized controlled trial and a few comparative retrospective clinical studies have addressed this issue. Laparoscopy reduces de novo adhesion formation but has no efficacy in reducing adhesion reformation after adhesiolysis. Moreover, several studies have suggested that the reduction of de novo post-operative adhesions does not seem to have a significant clinical impact. Experimental data in animal models have suggested that CO₂ pneumoperitoneum can cause acute peritoneal inflammation during laparoscopy depending on the insufflation pressure and the surgery duration. Broad peritoneal cavity protection by the insufflation of a low-temperature humidified gas mixture of CO₂, N₂O and O₂ seems to represent the best approach for reducing peritoneal inflammation due to pneumoperitoneum. However, these experimental data have not had a significant impact on the modification of laparoscopic instrumentation. In contrast, surgeons should train themselves to perform laparoscopy quickly, and they should complete their learning curves before testing chemical anti-adhesive agents and anti-adhesion barriers. Chemical anti-adhesive agents have the potential to exert broad peritoneal cavity protection against adhesion formation, but when these agents are used alone, the concentrations needed to prevent adhesions are too high and could cause major post-operative side effects. Anti-adhesion barrier