A low mortality, high morbidity Reduced Intensity Status Epilepticus (RISE) model of epilepsy and epileptogenesis in the rat

Animal models of acquired epilepsies aim to provide researchers with tools for use in understanding the processes underlying the acquisition, development and establishment of the disorder. Typically, following a systemic or local insult, vulnerable brain regions undergo a process leading to the development, over time, of spontaneous recurrent seizures. Many such models make use of a period of intense seizure activity or status epilepticus, and this may be associated with high mortality and/or global damage to large areas of the brain. These undesirable elements have driven improvements in the design of chronic epilepsy models, for example the lithium-pilocarpine epileptogenesis model. Here, we present an optimised model of chronic epilepsy that reduces mortality to 1% whilst retaining features of high epileptogenicity and development of spontaneous seizures. Using local field potential recordings from hippocampus in vitro as a probe, we show that the model does not result in significant loss of neuronal network function in area CA3 and, instead, subtle alterations in network dynamics appear during a process of epileptogenesis, which eventually leads to a chronic seizure state. The model’s features of very low mortality and high morbidity in the absence of global neuronal damage offer the chance to explore the processes underlying epileptogenesis in detail, in a population of animals not defined by their resistance to seizures, whilst acknowledging and being driven by the 3Rs (Replacement, Refinement and Reduction of animal use in scientific procedures) principles

Depression of glutamate and GABA release by presynaptic GABAB receptors in the entorhinal cortex in normal and chronically epileptic rats

Presynaptic GABAB receptors (GABABR) control glutamate and GABA release at many synapses in the nervous system. In the present study we used whole-cell patch-clamp recordings of spontaneous excitatory and inhibitory synaptic currents in the presence of TTX to monitor glutamate and GABA release from synapses in layer II and V of the rat entorhinal cortex (EC)in vitro. In both layers the release of both transmitters was reduced by application of GABABR agonists. Quantitatively, the depression of GABA release in layer II and layer V, and of glutamate release in layer V was similar, but glutamate release in layer II was depressed to a greater extent. The data suggest that the same GABABR may be present on both GABA and glutamate terminals in the EC, but that the heteroreceptor may show a greater level of expression in layer II. Studies with GABABR antagonists suggested that neither the auto- nor the heteroreceptor was consistently tonically activated by ambient GABA in the presence of TTX. Studies in EC slices from rats made chronically epileptic using a pilocarpine model of temporal lobe epilepsy revealed a reduced effectiveness of both auto- and heteroreceptor function in both layers. This could suggest that enhanced glutamate and GABA release in the EC may be associated with the development of the epileptic condition. Copyright © 2006 S. Karger AG

Strength and reliability properties of glass frit bondet micro packages

The hermetic package is one crucial element to ensure high reliability and lifetime of micro mechanical sensors in automotive applications. In a proactive approach fundamental reliability limiting effects are investigated. The bond quality of aged samples is characterised by Weibull analysis of tensile tested samples. By FE analysis the three dimensional stress distribution in the bond frame during tensile testing is evaluatet using the maximum principal stresses determined by experimentally obtained fracture forces. The Micro-Chevron-Test is applied for the first time to samples containing an intermediate glass frit layer. A meande ring crack path is observed and the fracture toughness is determined

Optimiertes Einwachsverhalten bei isoelastischen Titanimplantaten durch maßgeschneiderte, elektrophoretisch hergestellte Hydroxylapatit(HAP)-Schichten

Ziel des Gesamtprojektes ist die Entwicklung eines maßgeschneiderten Verbundwerkstoffes, der für verschiedene Implantattypen, wie Hüftendoprothesen, Kniegelenke, dentale Implantate usw. eingesetzt werden kann. Das Verbundsystem soll die günstigen Eigenschaften eines metallischen Werkstoffes (strukturelle Belastbarkeit auch beim Auftreten von Zugspannungen) und die einer Hydroxylapatit-(HAP)-Keramik (Bioaktivität und große Spaltüberbrückungsleistung) miteinander vereinen. Dabei soll der biokompatible metallische Werkstoff (Titanbasislegierung) oberflächlich durch Poren so strukturiert sein, daß ein möglichst isoelastisches Verhalten zum Knochen entsteht, wodurch eine Knochenneubildung durch gute Lastübertragung stimuliert und eine gute Verankerung gewährleistet wird. Durch Diffusionsglühen soll eine chemische Bindung und damit eine hohe Haftfestigkeit der Beschichtung erzielt werden. Um die Dauerfestigkeit des Substrates nicht negativ zu beeinflussen, müssen die entsprechenden Glühungen unterhalb der (alpha+beta)/beta-Umwandlungstemperatur erfolgen

Fracture mechanical life-time investigation of glass-frit bonded MEMS sensors

The long-term mechanical stability of the wafer level package is an important aspect in the reliability approach of MEMS products.Glass frit bonding is one of the most widely used bonding technologies. Since the glass frit bond frame is subjected to thermal stresses due to different thermal expansion coefficients of glass and silicon it constitutes a potential weak link of the package. Therefore, a reliability approach of a glass frit bonded MEMS device has to consider carefully its possible long term failure mechanisms. In particular, crack corrosion of the glass intermediate layer might lead to delayed failure of the device. In this paper, newly developed fracture mechanical measurement techniques as well as the numerical modelling of the experiments that allow determination of the fracture toughness and the crack growth rates of glass frit bonded micro samples are presented. A first fracture mechanical lifetime approach based on subcritical crack growth of initial defects in the glass frit bond frame is discussed. The obtained results form the basis for the lifetime prediction of glass frit bonded MEMS devices