1,721,011 research outputs found
Delayed-type hypersensitivity lesions in the central nervous system are prevented by inhibitors of matrix metalloproteinases
No full textWe have studied the effect of an inhibitor of matrix metalloproteinases, BB-1101, on a delayed-type hypersensitivity (DTH) response in the CNS. We used a recently described model in which heat-killed bacillus Calmette-Guerin (BCG) sequestered behind the blood-brain barrier (BBB) is targeted by a T-cell mediated response after subcutaneous injection of BCC (Matyszak and Perry, 1995). The DTH lesions are characterised by breakdown of the BBB, macrophage and lymphocyte infiltration and tissue damage including myelin loss. Treatment with BB-1101, which is not only a potent inhibitor of matrix metalloproteinases but also strongly inhibits TNF-α release, dramatically attenuated the CNS lesions. Breakdown of the BBB and the recruitment of T-cells into the site of the lesion were significantly reduced. There were many fewer inflammatory macrophages in DTH lesions than in comparable lesions from untreated animaIs. There was also significantly less myelin damage (assessed by staining with anti-MBP antibody). The DTH response in animals treated with dexamethasone was also reduced, but o a lesser degree. No significant effect was seen after administration of pentoxifylline, a phosphodiesterase inhibitor with effects including the inhibition of TNF-α production. Our results suggest that inhibitors of matrix metalloproteinases may be of considerable therapeutic benefit in neuroinflammatory diseases.</p
Dendritic competition: competition for what?
No full textA lesion to the retina of a newborn rat results in the retrograde degeneration of ganglion cells in a sector of retina peripheral to the lesion. The dendritic tree of ganglion cells bordering the region depleted of ganglion cells have their dendrites preferentially directed into this area. We have examined the factors which play a role in this rearrangement of the dendritic tree. The results show that the lesion in neonates selects for or produces a population of cells with the axon directed away from the depleted area and primary dendrites directed towards the depleted area. The abnormal dendritic bias cannot be accounted for solely on the basis of a decrease in contact inhibition since a reduction in the density of all ganglion cells by 30% prior to making the retinal lesion does not attenuate the abnormal dendritic bias into the depleted area. The abnormal dendritic bias is present in animals operated on up to 15 days of age postnatally but not in more mature animals. The abnormal dendritic bias develops prior to the formation of a large number of synapses in the inner nuclear layer. Our results cannot be easily accounted for by competition for synaptic contacts or a loss of contact inhibition as previously suggested. We propose that chemotropic factors produced within the area depleted of ganglion cells induce the abnormal dendritic bias and the number of synaptic contacts may limit the size of the dendritic field.</p
Functional lamination in the ganglion cell layer of the macaque's retina
No full textClose to the fovea of the primate retina the ganglion cell layer is at its maximal thickness and several layers of cells deep. In whole-mount preparations in which the ganglion cells had been retrogradely labelled to reveal the dendritic trees we have studied the distribution of the different ganglion cell types across the depth of the ganglion cell layer. The ganglion cells which project to the parvocellular layers (P ganglion cells) arc found more vitread than those which project to the magnoccllular layers (M ganglion cells). The cells which project to the midbrain lie in the outer part of the ganglion cell layer among the M cells and adjacent to the inner plexiform layer. Within the P and M classes of ganglion cell the On-centre cells lie more vitread than the Off-centre cells. These results are discussed with relation to the proportions of different cell types sampled with intraocular recordings from ganglion cells and the possible significance for the development of different tvpes of ganglion cell.</p
Turnover of resident microglia in the normal adult mouse brain
No full textWe undertook this study to determine whether the microglia, the resident macrophages of the central nervous system, turn over in the steady-state. The turnover of brain macrophages would lend support to the "Trojan Horse" hypothesis of central nervous system infection, since one origin of replacement cells is the circulating monocyte pool. We combined the immunohistochemical detection of F4/80, a specific macrophage marker, with [3H]thymidine incorporation and autoradiography in normal adult mice. We could detect double-labelled cells in the brains of mice perfused 60 min after isotope administration. Such cells were few in number, randomly scattered throughout the brain and had the morphology of typical resident cells. The labelling index at this survival time was 0.052 ± 0.003%. Thus resident microglia can synthesise DNA in situ. After longer survival times, we detected larger numbers of double-labelled cells. F4/80+ cells with resident morphology, mitotic figures, pairs of closely apposed (daughter) cells and cells with rounded macrophage-like morphology, all exhibited silver labelling. Twenty-four hours after isotope administration the labelling index was 0.192 ± 0.052%. From morphologic evidence and comparison of labelling indices at different survival times, we concluded that: 1. (i) resident microglia can synthesise DNA and go on to divide in situ; 2. (ii) cells are recruited from the circulating monocyte pool through an intact blood-brain barrier and rapidly differentiate into resident microglia. We estimate that the two processes contribute almost equally to the steady-state turnover of resident microglia.</p
A comparison of leucocyte responses to heat‐killed bacillus Calmette‐Guérin in different CNS compartments
No full textWe have previously shown that heat-killed bacillus Calmette-Guérin (BCG) injected into the CNS parenchyma does not produce a typical delayed-type hypersensitivity (DTH) response [23]. In this paper we have compared the initial leucocyte response in the CNS parenchyma, ventricles and skin to gain insight into the mechanisms by which the DTH response in the CNS might be controlled. We have found that 105 organisms of heat-killed BCG injected into either the CNS parenchyma or the lateral ventricles produced a rapid neutrophil response at the site of the injection, which was comparable with that in the skin. The neutrophil response resolved within the first week. Unlike the neutrophil response, the mononuclear phagocyte response in the CNS parenchyma was much smaller than that seen in the ventricles and the skin and it resolved within 4 weeks. Furthermore, the myelomonocytic response in the CNS parenchyma failed to clear the BCG. The acute inflammatory response in the choroid plexus/ventricles and skin developed with a similar time-course into a typical DTH response. After the first week, lesions at these two sites were composed predominantly of T-cells and macrophages. DTH lesions were still detected at both sites after 6 weeks.The failure of the immune system to recognize foreign antigens sequestrated in the CNS parenchyma may have significant implications especially in studies of inflammatory responses in the CNS of unknown origin.</p
Activation and Proliferation of Murine Microglia are Insensitive to Glucocorticoids in Wallerian Degeneration
No full textActivation and proliferation of microglia are commonly described in the central nervous system after a wide range of insults, but the mechanisms that regulate their phenotype in vivo are still poorly understood. We have studied the effect that adrenalectomy and dexamethasone treatment have on the proliferation and activation of microglia during Wallerian degeneration of the optic nerve in BALB/c mice. We found that the onset and rate of microglia proliferation is independent of glucocorticoids. There was an increase in F4/80-positive cells 3 days after optic nerve crush, with a peak at 7 days, both in the optic nerve and its target, the superior colliculus. The numbers of F4/80-positive cells remained high up to 3 weeks after crush, the longest time point examined. We also found that up-regulation of F4/80 and the complement receptor type 3 and expression of major histocompatibility complex class II antigens were not affected by adrenalectomy or dexamethasone treatment. These observations show that, unlike microglia in vitro or peripheral macrophages, microglia do not readily respond to glucocorticoids, which could indicate a lack of or reduced expression of glucocorticoid receptor in these cells.</p
Evidence for an early inflammatory response in the central nervous system of mice with scrapie
No full textIn Alzheimer's disease, the most prevalent of the neurodegenerative diseases, inflammation of the CNS contributes to the pathology and is a target for therapy. In contrast, the group of neurodegenerative conditions known as the Prion Diseases have been widely reported as lacking any inflammatory elements despite the many similarities between the pathologies of Alzheimer's Disease and Prion Diseases? We have found evidence for an inflammatory component in mouse scrapie, characterized by microglial activation and T-lymphocyte recruitment, which appears long before any clinical signs of the disease and spreads along well-defined anatomical pathways. These observations emphasize the potential value of murine scrapie as a model for studying the inflammatory pathology of other neurodegenerative diseases.</p
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
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