1,721,273 research outputs found
Effects of recombinant tissue plasminogen activator after intraluminal thread occlusion in mice - Role of hemodynamic alterations
No full textBackground and Purpose-It has been suggested that recombinant tissue plasminogen activator (rtPA) may cause an aggravation of injury after transient focal ischemia via excitotoxic side effects. Such rtPA toxicity would be of major clinical significance since rtPA is increasingly used in stroke treatment. This study was conducted to evaluate the effects of dose, application time, and hemodynamic changes after intravenous rtPA treatment in focal ischemia. Methods-Mice were subjected to a 90-minute episode of middle cerebral artery thread occlusion, and rtPA effects were assessed by laser-Doppler flowmetry, [C-14]iodoantipyrine autoradiography, and triphenyltetrazolium chloride staining. Results and Conclusions-We provide evidence that rtPA provokes complex hemodynamic alterations in the ischemic brain tissue, which include an initial hyperperfusion and a more delayed hypoperfusion response. Changes are most pronounced in the periphery of the ischemic infarct, where regional blood flow drops below critical thresholds of tissue viability. Our observations suggest that changes of perfusion may at least partly explain the rtPA-induced increase of infarct size, which has previously been reported and which we also confirmed in the present experiments. Notably, both the secondary hypoperfusion and increase of infarct volume were abolished when rtPA-treated animals received additional heparin infusions. This finding suggests that a secondary hypercoagulability may compromise brain perfusion after rtPA delivery. Accordingly, early treatment with heparin might help to prevent the rtPA-induced changes
Human synapsin 1 gene promoter confers highly neuron-specific long-term transgene expression from an adenoviral vector in the adult rat brain depending on the transduced area
No full textTargeting therapeutic transgene expression to defined tissues is a major task in the development of safe and efficient gene therapy protocols. Recombinant adenovirus is an attractive vector because it can be prepared in huge quantity and new generation vectors possess very large cloning capacities combined with reduced immunogenicity. In the brain, adenovirus transduces mainly glial cells, making it difficult to use this vector system in applications that need expression of therapeutic proteins in neurons. Here, we show that by using a small fragment of the human synapsin 1 gene promoter, we were able to restrict transgene expression from an adenoviral vector exclusively to neurons. Furthermore, we obtained stable long-term transgene expression from this vector in striatum and thalamus at appropriate vector dose. Other promoters like the CMV and U1snRNA promoters also mediated transgene expression over several months, but mainly in glial cells. Although the NSE promoter was relatively neuron specific, it still expressed in glial cells also, and was clearly outperformed by the synapsin promoter with respect to transcriptional neuronal targeting. As an important feature of adenoviral-mediated gene transfer to the brain, we demonstrate that dopaminergic neurons of the substantia nigra do not allow for long-term expression from adenoviral vectors. Strikingly, these neurons appeared to specifically attenuate transgene expression by deleting the adenoviral genome
Rifampicin attenuates brain damage in focal ischemia
No full textRifampicin is an antibacterial agent that is widely used in tuberculosis and leprosy therapy. Interestingly, some experimental studies indicate that rifampicin acts as a hydroxyl radical scavenger and a glucocorticoid receptor activator. In this study, the neuroprotective effect of rifampicin was evaluated after transient and permanent focal cerebral ischemia. Anaesthetized mate C57BL/6j mice were submitted to permanent or transient thread occlusion of the middle cerebral artery (MCA). Reperfusion in transient ischemia was initiated 30 min later by thread retraction. Rifampicin or vehicle were applied intraperitoneally before permanent or immediately after 30 min of transient ischemia . Later, 24 It after permanent or transient ischemia, animals were re-anesthetized and decapitated. Brain injury was evaluated by triphenyltetrazolium chloride staining (TTC), terminal transferase biotinylated-dUTP nick end labeling TUNEL and cresyl violet staining. A 20-mg/kg sample of rifampicin showed a significant neuroprotection after cerebral ischemia. The number of TUNEL-positive cells in the striatum, where disseminated tissue injury was observed, was also reduced by application of rifampicin as compared with vehicle-treated animals. The present report shows that administration of rifampicin efficiently reduces brain injury after permanent and transient focal cerebral ischemia in mice. (C) 2003 Elsevier B.V. All rights reserved
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
Rifampicin inhibits neurodegeneration in the optic nerve transection model in vivo and after 1-methyl-4-phenylpyridinium intoxication in vitro
No full textRifampicin is an antibacterial drug which is highly effective in the treatment of tuberculosis and leprosy. It has been shown to exert antioxidative as well as anti-apoptotic effects. In this study, the neuroprotective effect of rifampicin was examined after 1-methyl-4-phenylpyridinium (MPP+)-induced dopaminergic cell death in vitro, and on the survival of retinal ganglion cells after optic nerve transection in vivo. Rifampicin administration significantly increased the number of surviving dopaminergic neurons after MPP+ intoxication as compared to control cultures. No cytotoxic effects were noted even at final rifampicin concentrations of 100 muM. In the rifampicin-treated group, retinal ganglion cell survival was significantly increased after axotomy as compared with vehicle-treated and phosphate-buffered saline-treated control animals. These results suggest that rifampicin is able to prevent neuronal degeneration in cell death paradigms involving oxidative stress and activation of apoptotic pathways. It may thus play a role in the future treatments of neurodegenerative disorders
Effects of pinealectomy and melatonin on the retrograde degeneration of retinal ganglion cells in a novel model of intraorbital optic nerve transection in mice
No full textThe effects of pinealectomy and of intraperitoneally administered melatonin on the retrograde degeneration of retinal ganglion cells (RGCs) were examined in a novel model of optic nerve (ON) transection in C57BL/6J mice. RGCs were prelabeled with the fluorescent tracer 1,1'-dioctadecyl-3,3,3',3'-tetramethyl indocarbocyanine perchlorate (Di-I), and the ON was cut inside the orbital cavity 7 days later. The degree of RGC injury was assessed by counting viable Di-I labeled RGCs in various locations of the retina. In unlesioned control eyes, a mean ganglion cell density of 1891 +/- 30/mm(2) (mean +/- S.E.M.) was determined. The cell density markedly declined at 14 days after axotomy (295 +/- 9 cells/mm(2); 15.6% of contralateral). Sham-pinealectomy did not influence the density of RGCs at 14 days after ON transection (382 +/- 37 cells/mm(2)). In pinealectomized animals, on the other hand, the RGC number was significantly reduced as compared with untreated and sham-pinealectomized animals (91 +/- 33 RGCs/mm(2)). The effect of pinealectomy was reversed after i.p. administration of melatonin (4 mg/kg bw bolus followed by continuous infusion of 8 mg/kg bw/day) (286 +/- 27 cells/mm(2)) In nonpinealectomized. animals., on the contrary, i.p. melatonin did not influence the RGC density (344 +/- 20 cells/mm(2)). The present results suggest that endogenous melatonin prevents the delayed degeneration of adult central nervous system (CNS) neurons in vivo, and that exogenous substitution of melatonin may be useful to protect injured neurons against cell death under conditions of melatonin deficiency, e.g. in the aged brain, when melatonin synthesis and secretion have decreased
Inhibition of neuronal apoptosis in vitro and in vivo using TAT-Mediated protein transduction
No full textThe HIV TAT protein contains an 11-amino-acid protein transduction domain which acts as a "Trojan peptide": Linked to other macromolecules, it carries them across cellular membranes. Here, we demonstrate for the first time that fusion of the TAT protein transduction domain to an antiapoptotic protein represents a feasible technique to rescue neurons from apoptotic degeneration in vitro and in vivo. When fused to the antiapoptotic protein Bcl-X-L it mediated uptake of the fusion protein into neurons. Once inside the cells, TAT-Bcl-X-L was stable for many days and maintained its antiapoptotic function. It completely blocked low-potassium-induced apoptosis of cerebellar granule cells in vitro. In vivo, 24% of mouse retinal ganglion cells were prevented from undergoing retrograde neuronal apoptosis caused by optic nerve lesion when TAT-Bcl-X-L was intraocularly injected. The application of TAT fusion proteins may in the future greatly facilitate neuroprotective therapy strategies for neurological disorders
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