1,720,963 research outputs found
The influence of systemic inflammation on inflammation in the brain: implications for chronic neurodegenerative disease
No full textSystemic inflammation is associated with sickness behaviour and signals pass from the blood to the brain via macrophage populations associated with the brain, the perivascular macrophages and the microglia. The amplitude, or gain, of this transduction process is critically dependent on the state of activation of these macrophages. In chronic neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, or prion disease the pathology is associated with a highly atypical inflammatory response, characterised by the activation of the macrophage populations in the brain: the cells are primed. Recent evidence suggests that systemic inflammation may impact on local inflammation in the diseased brain leading to exaggerated synthesis of inflammatory cytokines and other mediators in the brain, which may in turn influence behaviour. These interactions suggest that systemic infections, or indeed any systemic challenge that promotes a systemic inflammatory response, may contribute to the outcome or progression of chronic neurodegenerative disease
Microglia activation in acute and chronic neurodegeneration and the impact of systemic infection
No full textMicroglia in the normal brain parenchyma are characterized by their downregulated or quiescent state. However, following almost any pathological insult to the brain they become activated and alter their morphology and upregulate their cell surface antigen expression. We have investigated the cytokine profile associated with acute and chronic neurodegeneration and microglia activation. We have shown that following acute injury to the brain, there is a period (24 h) of pro-inflammatory cytokine synthesis, but the microglia are morphologically activated for weeks. In murine prion disease pathology, a model of chronic neurodegeneration, the microglia are significantly increased in number and are morphologically activated. However, the cytokine profile is anti-inflammatory and dominated by TGFb. However, these activated microglia are primed, as a systemic challenge with endotoxin, to mimic a peripheral infection leads to enhanced cytokine synthesis and exaggerated behavioural sequelae. Interactions between systemic inflammation and an ongoing inflammatory response in the brain is relevant to many acute and chronic neurodegenerative conditions in human beings
Microglial physiology: unique stimuli, specialized responses
No full textMicroglia, the macrophages of the central nervous system parenchyma, have in the normal healthy brain a distinct phenotype induced by molecules expressed on or secreted by adjacent neurons and astrocytes, and this phenotype is maintained in part by virtue of the blood-brain barrier's exclusion of serum components. Microglia are continually active, their processes palpating and surveying their local microenvironment. The microglia rapidly change their phenotype in response to any disturbance of nervous system homeostasis and are commonly referred to as activated on the basis of the changes in their morphology or expression of cell surface antigens. A wealth of data now demonstrate that the microglia have very diverse effector functions, in line with macrophage populations in other organs. The term activated microglia needs to be qualified to reflect the distinct and very different states of activation-associated effector functions in different disease states. Manipulating the effector functions of microglia has the potential to modify the outcome of diverse neurological diseases
What is immune privilege (not)?
No full textThe ‘immune privilege’ of the central nervous system (CNS) is indispensable for damage limitation during inflammation in a sensitive organ with poor regenerative capacity. It is a longstanding notion which, over time, has acquired several misconceptions and a lack of precision in its definition. In this article, we address these issues and re-define CNS immune privilege in the light of recent data. We show how it is far from absolute, and how it varies with age and brain region. Immune privilege in the CNS is often mis-attributed wholly to the blood–brain barrier. We discuss the pivotal role of the specialization of the afferent arm of adaptive immunity in the brain, which results in a lack of cell-mediated antigen drainage to the cervical lymph nodes although soluble drainage to these nodes is well described. It is now increasingly recognized how immune privilege is maintained actively as a result of the immunoregulatory characteristics of the CNS-resident cells and their microenvironment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Enhanced survival in Sandhoff disease mice receiving a combination of substrate deprivation therapy and bone marrow transplantation
No full textSandhoff disease is a lysosomal storage disorder characterized by GM2 ganglioside accumulation in the central nervous system (CNS) and periphery. It results from mutations in the HEXB gene, causing a deficiency in ?-hexosaminidase. Bone marrow transplantation (BMT), which augments enzyme levels, and substrate deprivation (using the glycosphingolipid biosynthesis inhibitor N-butyldeoxynojirimycin [NB-DNJ]) independently have been shown to extend life expectancy in a mouse model of Sandhoff disease. The efficacy of combining these 2 therapies was evaluated. Sandhoff disease mice treated with BMT and NB-DNJ survived significantly longer than those treated with BMT or NB-DNJ alone. When the mice were subdivided into 2 groups on the basis of their donor bone marrow-derived CNS enzyme levels, the high enzyme group exhibited a greater degree of synergy (25%) than the group as a whole (13%). Combination therapy may therefore be the strategy of choice for treating the infantile onset disease variants
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