4-Aminopyridine-induced epileptogenesis depends on activation of mitogen-activated protein kinase ERK

Extracellular signal-regulated kinases such as ERK1 [p44 mitogen-activated protein kinase (MAPK)] and ERK2 (p42 MAPK) are activated in the CNS under physiological and pathological conditions such as ischemia and epilepsy. Here, we studied the activation state of ERK1/2 in rat hippocampal slices during application of the K+ channel blocker 4-aminopyridine (4AP, 50 lM), a procedure that enhances synaptic transmission and leads to the appearance of epileptiform activity. Hippocampal slices superfused with 4AP-containing medium exhibited a marked activation of ERK1/2 phosphorylation that peaked within about 20 min. These effects were not accompanied by changes in the activation state of c-Jun N-terminal kinase (JNK), another member of the MAP kinase superfamily. 4AP-induced ERK1/2 activation was inhibited by the voltage-gated Na+ channel blocker tetrodotoxin (1 lM). We also found that application of the ERK pathway inhibitors U0126 (50 lM) or PD98059 (100 lM) markedly reduced 4AP-induced epileptiform synchronization, thus abolishing ictal discharges in the CA3 area. The effects induced by U0126 or PD98059 were not associated with changes in the amplitude and latency of the field potentials recorded in the CA3 area following electrical stimuli delivered in the dentate hylus. These data demonstrate that activation of ERK1/2 accompanies the appearance of epileptiform activity induced by 4AP and suggest a cause-effect relationship between the ERK pathway and epileptiform synchronization

Avalanches in a Stochastic Model of Spiking Neurons

Neuronal avalanches are a form of spontaneous activity widely observed in cortical slices and other types of nervous tissue, both in vivo and in vitro. They are characterized by irregular, isolated population bursts when many neurons fire together, where the number of spikes per burst obeys a power law distribution. We simulate, using the Gillespie algorithm, a model of neuronal avalanches based on stochastic single neurons. The network consists of excitatory and inhibitory neurons, first with all-to-all connectivity and later with random sparse connectivity. Analyzing our model using the system size expansion, we show that the model obeys the standard Wilson-Cowan equations for large network sizes ( neurons). When excitation and inhibition are closely balanced, networks of thousands of neurons exhibit irregular synchronous activity, including the characteristic power law distribution of avalanche size. We show that these avalanches are due to the balanced network having weakly stable functionally feedforward dynamics, which amplifies some small fluctuations into the large population bursts. Balanced networks are thought to underlie a variety of observed network behaviours and have useful computational properties, such as responding quickly to changes in input. Thus, the appearance of avalanches in such functionally feedforward networks indicates that avalanches may be a simple consequence of a widely present network structure, when neuron dynamics are noisy. An important implication is that a network need not be “critical” for the production of avalanches, so experimentally observed power laws in burst size may be a signature of noisy functionally feedforward structure rather than of, for example, self-organized criticality

Lateralization of mesial temporal lobe epilepsy with chronic ambulatory electrocorticography

OBJECTIVE: Patients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions. METHODS: Ambulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded. RESULTS: Eighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording. SIGNIFICANCE: About one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions

Nowe wyroby walcowane ze stopów aluminium dla przemysłu motoryzacyjnego

Clad aluminium strips are used in the automotive industry to manufacture parts of heat exchangers. They are characterised by favourable strength properties, good corrosion resistance and susceptibility to plastic deformation, and can undergo surface brazing at a temperature of about 600°C. As a result of studies, the properties of alloys for the production of clad strips have been optimised. Optimising covered the alloy chemical composition and selected parameters such as the metal condition, the mechanical properties and anti-corrosion behaviour, including the methods for corrosion potential equalisation and sacrificial protection. The obtained technological results of the clad aluminium strip production were verified under the industrial conditions of Impexmetal Huta Aluminium Konin S.A. In a laboratory of the Institute of Non-Ferrous Metals (IMN), the clad strips were tested for the pre-assumed functional properties. Mechanical properties were tested, and the structure and corrosion behaviour were characterised. The reactivity of the clad layer was analysed under different technological conditions. The thermal bond produced by these clad layers was tested by simulation of the heat exchanger manufacturing process. As a result of the conducted research it has been found that all the essential characteristics of the clad strips produced under domestic conditions are in no way different from the properties of imported strips, while modification of the alloy chemical composition has contributed to the effective sacrificial protection of heat exchangers made from these strips. Clad aluminium strips are now successfully produced by the domestic aluminium industry. The improvement of materials used for the heat exchangers can contribute to the reduced overall dimensions of these products and increased efficiency, thus leading to energy savings. The results were obtained within the framework of the Task No. ZPB/38/66716/IT2/10 executed as part of the „IniTech” Project.Aluminiowe taśmy platerowane znajdują zastosowanie w przemyśle motoryzacyjnym do produkcji elementów wymienni- ków ciepła. Charakteryzują się one korzystnymi właściwościami wytrzymałościowymi, dobrą odpornością na korozję i podatno- ścią do odkształcenia plastycznego oraz zdolnością do zgrzewania powierzchniowego w temperaturze około 600°C. W wyniku badań dokonano optymalizacji właściwości stopów przeznaczonych do produkcji taśm platerowanych. Zoptymalizowano skład chemiczny stopów oraz wybrane parametry takie jak stan materiału, właściwości mechaniczne i antykorozyjne z uwzględ- nieniem metody wyrównania potencjałów korozyjnych oraz metody ochrony protektorowej. Efekty technologii platerowanych taśm aluminiowych zostały pozytywnie zweryfikowane w warunkach przemysłowych Impexmetal S.A. Huta Aluminium Konin W warunkach laboratoryjnych IMN przetestowano wytworzone taśmy pod kątem założonych własności użytkowych. Zbadano własności mechaniczne taśm. scharakteryzowano ich strukturę i właściwości korozyjne. Dokonano analizy reaktywności plateru w różnych warunkach technologicznych oraz zbadano wytworzone z ich udziałem połączenia termiczne w warunkach symulacji procesu produkcji wymienników ciepła W wyniku przeprowadzonych badań stwierdzono, że wszystkie istotne właściwości taśm platerowanych wytworzonych w warunkach krajowych nie różnią się od właściwości taśm importowanych, a odpowiednia modyfikacja składu chemicznego stopów pizyczyniła się do zapewnienia skutecznej ochrony protektorowej wymienników cie- pła wytwarzanych z tych taśm. Aluminiowe taśmy platerowane wytwarzane są obecnie w krajowym przemyśle aluminiowym. Ulepszenie materiałów stosowanych do konstrukcji wymienników ciepła przyczynić się może do zmniejszenia gabarytów wy- mienników ciepła i zwiększenia ich sprawności, co prowadzić powinno do oszczędności energii. Wyniki uzyskano w Projekcie nr ZPB/38/66716/1T2/10 zrealizowanym w ramach przedsięwzięcia "IniTech”