1,720,976 research outputs found
Systemic inflammation alters satellite glial cell function and structure : a possible contribution to pain
No full textLocal peripheral injury activates satellite glial cells (SGCs) in sensory ganglia, which may contribute to chronic pain. We hypothesized that systemic inflammation affects sensory ganglia like local injury. We induced systemic inflammation in mice by injecting lipopolysaccharide (LPS) intraperitoneally, and characterized SGCs and neurons in dorsal root ganglia (DRG), using dye injection, calcium imaging, electron microscopy (EM), immunohistochemistry, and electrical recordings. Several days post-LPS, SGCs were activated, and dye coupling among SGCs increased 3-4.5-fold. EM showed abnormal growth of SGC processes and the formation of new gap junctions. Sensitivity of SGCs to ATP increased twofold, and neuronal excitability was augmented. Blocking gap junctions reduced pain behavior in LPS-treated mice. Thus, changes in DRG due to systemic inflammation are similar to those due to local injury, which may explain the pain in sickness behavior and in other systemic diseases
Glial coupling in systemic insults : possible contribution to chronic pain
No full textChronic pain is a major clinical problem, but the mechanisms underlying it are still rather obscure, and therapies, which are targeted to neurons, are largely ineffective. There is evidence that central glial cells are altered in pain models, and that these cells can be an effective therapeutic target. We have shown that gap junction (GJ)- mediated coupling among satellite glial cells (SGCs) in sensory ganglia, increased 5-7 fold in mouse pain models, and that blocking GJs reduces pain behavior. Previous work has focused on local injuries such as axotomy, and here we asked whether similar mechanisms operate in systemic insults that cause pain. Using mice, we induced systemic inflammation with lipopolysaccharide (LPS, 2.5 mg/kg), and also produced neuropathy using the cancer drug oxaliplatin (2x4 mg/kg, 3 days apart). Intracellular injections of Lucifer yellow showed that both LPS and oxaliplatin induced a large increase in SGC coupling in dorsal root ganglia. Electron microscopy revealed that LPS induced the formation of bridges between SGCs, where these cells were connected by newly-formed GJs. The expression of the glial marker glial fibrillary acidic protein (GFAP) was enhanced (the number of neurons surrounded by GFAP-positive cells increased 3-fold), consistent with glial activation. Both treatments also caused augmented tactile sensitivity, as tested with von Frey filaments. These changes persisted for about two weeks. Systemic (IP) injection of the GJ blocker carbenoxolone (50 mg/kg), was so far done only after oxaliplatin, and clearly reduced the behavioral pain responses. Following LPS injection, there was a large increase in the sensitivity of SGCs to ATP, acting on P2 receptors. As both GJ and P2 receptors participate in the propagation of calcium waves, the enhanced GJ communication and P2 upregulation may underlie augmented spread of signals within the ganglion. We conclude that local and systemic insults share fundamental similarities in that both induce SGC activation. Furthermore, activation is associated with a large increase in SGC coupling. We propose that glial coupling contributes to chronic pain, and that a potential therapy for pain is the selective blockade of GJ
Long term effects of lipopolysaccharide on satellite glial cells in mouse dorsal root ganglia.
No full textLipopolysaccharide (LPS) has been used extensively to study neuroinflammation, but usually its effects were examined acutely (24 h<). We have shown previously that a single intraperitoneal LPS injection activated satellite glial cells (SGCs) in mouse dorsal root ganglia (DRG) and altered several functional parameters in these cells for at least one week. Here we asked whether the LPS effects would persist for 1 month. We injected mice with a single LPS dose and tested pain behavior, assessed SGCs activation in DRG using glial fibrillary acidic protein (GFAP) immunostaining, and injected a fluorescent dye intracellularly to study intercellular coupling. Electron microscopy was used to quantitate changes in gap junctions. We found that at 30 days post-LPS the threshold to mechanical stimulation was lower than in controls. GFAP expression, as well as the magnitude of dye coupling among SGCs were greater than in controls. Electron microscopy analysis supported these results, showing a greater number of gap junctions and an abnormal growth of SGC processes. These changes were significant, but less prominent than at 7 days post-LPS. We conclude that a single LPS injection exerts long-term behavioral and cellular changes. The results are consistent with the idea that SGC activation contributes to hyperalgesi
Glial cell coupling and growth in sensory ganglia after axotomy : ultrastructural evidence
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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
Satellite cell reactions to axon injury of sensory ganglion neurons: increase in number of gap junctions and formation of bridges connecting previously separate perineuronal sheaths
No full textThis study investigated satellite cell changes in mouse L4 and L5 spinal ganglia 14 days after unilateral transection of sciatic and saphenous nerves. The ganglia were studied under the electron microscope in single and serial sections, and by dye injection. Satellite cell responses to axon injury of the neurons with which they are associated included the formation of bridges connecting previously separate perineuronal sheaths and the formation of new gap junctions, resulting in more extensive cell coupling. Some possible consequences of these satellite cell reactions are briefly discussed
Glial cell plasticity in sensory ganglia induced by nerve damage
No full textNumerous studies have been done on the effect of nerve injury on neurons of sensory ganglia but little is known about the contribution of satellite glial cells (SCs) in these ganglia to post-injury events. We investigated cell-to-cell coupling and ultrastructure of SCs in mouse dorsal root ganglia after nerve injury (axotomy). Under control conditions SCs were mutually coupled, but mainly to other SCs around a given neuron. After axotomy SCs became extensively coupled to SCs that enveloped other neurons, apparently by gap junctions. Serial section electron microscopy showed that after axotomy SC sheaths enveloping neighboring neurons formed connections with each other. Such connections were absent in control ganglia. The number of gap junctions between SCs increased 6.5-fold after axotomy. We propose that axotomy induces growth of perineuronal SC sheaths, leading to contacts between SCs enveloping adjacent neurons and to formation of new gap junctions between SCs. These changes may be an important mode of glial plasticity and can contribute to neuropathic pain
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
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