1,720,975 research outputs found
The Pilocarpine Model of Mesial Temporal Lobe Epilepsy: Over One Decade Later, with More Rodent Species and New Investigative Approaches
No full textFundamental work on the mechanisms leading to focal epileptic discharges in mesial temporal
lobe epilepsy (MTLE) often rests on the use of rodent models in which an initial status epilepticus (SE) is induced by kainic acid or pilocarpine. In 2008 we reviewed how, following systemic
injection of pilocarpine, the main subsequent events are the initial SE, the latent period, and the
chronic epileptic state. Up to a decade ago, rats were most often employed and they were
frequently analysed only behaviorally. However, the use of transgenic mice has revealed novel
information regarding this animal model. Here, we review recent findings showing the existence
of specific neuronal events during both latent and chronic states, and how optogenetic activation
of specific cell populations modulate spontaneous seizures. We also address neuronal damage
induced by pilocarpine treatment, the role of neuroinflammation, and the influence of circadian
and estrous cycles. Updating these findings leads us to propose that the rodent pilocarpine model
continues to represent a valuable tool for identifying the basic pathophysiology of MTLE
Untersuchungen zur funktionellen Rolle veränderter Expression und Verteilung von Ionenkanälen und Neurotransmitter-Rezeptoren bei fokaler Epilepsie unter Verwendung transgener Tiermodelle
Get PDFDie hier dargestellten molekularpathologischen und phänotypischen Untersuchungen an transgenen Mäusen in einem Epilepsiemodel für TLE verdeutlichen die funktionelle Relevanz erworbener Veränderungen der Verteilung und Expression der (a) mGluR1 und mGluR4 Neurotransmitter-Rezeptoren sowie (b) des spannungsabhängigen T-Typ-Ca2+-Kanals Cav3.2 für mehrere pathogenetisch zentrale Aspekte der TLE. Eine elementare Voraussetzung für die Untersuchung der Unterschiede von Anfallsstärke und -frequenz der transgenen Tiere war die im Rahmen dieser Arbeit etablierte permanente EEG- und Video-Analyse von Mäusen.Für die mGluR1-Untereinheit zeigte sich, dass eine hippokampal verstärkte Expression mit einer vermehrten chronischen Anfallsneigung vergesellschaftet ist. Die Expression von mGluR4 hingegen vermittelt sowohl einen antiepileptischen Effekt im akuten Anfallsstadium nach Status epilepticus als auch eine neuroprotektive Wirkung. Diese Prozesse stellen sich als aberrierende, erworbene synaptische Plastizität nach Status epilepticus dar.
In Cav3.2-defizienten Mäusen waren fundamentale Effekte im Hinblick auf hippokampale Schädigung sowie chronisches Anfallsgeschehen zu beobachten. Das grundlegend veränderte Entladungsverhalten hippokampaler Nervenzellen mit erhöhter Neigung zu salvenartigen Entladungen basierend auf vermehrter Transkription von Cav3.2 ist mit einer verstärkten Frequenz und Schwere chronisch rekurrenter Anfälle sowie erheblich ausgeprägterem hippokampalem Nervenzellverlust verbunden. Durch die benannte Veränderung ihres Entladungsverhaltens können die entsprechenden CA1-Neurone zu spontanen Schrittmachern epileptischer Netzwerkentladung werden. Solche Veränderungen spiegeln wesentliche funktionelle Konsequenzen einer erworbenen intrinsischen Ionenkanalopathie in der Epileptogenese wider.
Die veränderte Regulation und Expression verschiedener Rezeptoren und Kanäle in neuronalen Verschaltungen scheinen eine entscheidende Rolle für die Entwicklung und Ausprägung der chronischen Epilepsie zu spielen. Initiale Fehlregulationen im Rahmen eines SE oder in der frühen Epileptogenese führen im Gehirn zu massiven irreversiblen Prozessen. Kompensatorische Mechanismen können dabei möglicherweise nicht mehr adäquat aktiviert werden, was unter Umständen zu einer Progression epileptogener Prozesse führen kann. In diesem Zusammenhang stellen die metabotropen Glutamatrezeptoren sowie die Cav3.2-Untereinheit wichtige Zielstrukturen für die künftige Entwicklung hochspezifischer Pharmaka dar.The results of the molecular and physiological analysis of transgenic mice in a model of temporal lobe epilepsy presented in this thesis show the functional importance of acquired alterations in the distribution and expression of (a) the metabotropic glutamate receptors mGluR1 and mGluR4 as well as (b) of the Cav3.2 subunit of the voltage dependent T-type calcium channel for several key aspects of TLE. The characterization of seizure severity and frequency of transgenic mice in a TLE model made the establishment of a permanent EEG and video monitoring unit an essential part of this thesis.
This study showed that an increased hippocampal expression of mGluR1 is associated with a propensity to seizures in the chronic phase. On contrast, expression of mGluR4 mediates anti-epileptic and neuroprotective effects in the acute phase after status epilepticus. These processes can be described as aberrant acquired synaptic plasticity after SE.
Mice deficient for Cav3.2 exhibited profound effects in regard to hippocampal damage and to the characteristics of the chronic phase. Neurons with a higher levels of Cav3.2 mRNA show a fundamentally altered firing behaviour with an increase in the propensity to burst and thereby can function as spontaneous pacemakers of epileptic networks. This results in an increase in the frequency and severity of recurrent chronic seizures as well as in a dramatic neuronal cell loss in the hippocampus. These changes represent the functional consequences of an acquired ion channelopathy during epileptogenesis.
Alterations in expression and distribution of various receptors and channels in neuronal networks seem to play an essential role in the development of chronic epilepsy. Initial disregulations as a consequence of SE or during early epileptogenesis can cause massive irreversible damage within the brain. Compensatory mechanisms might not be activated adequately and as a result epileptogenic processes might progress.In this respect, metabotropic glutamate receptors and the Cav3.2 subunit of voltage gated calcium channels might represent valuable targets for the future development of highly targeted pharmaca
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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