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  • Rat  (5)
  • Cerebral cortex  (4)
  • Bicuculline  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Comparison of the effects of losigamone and its isomers on maximal electroshock induced convulsions in mice and on three different patterns of low magnesium induced epileptiform activity in slices of the rat temporal cortex (1992)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 345 (1992), S. 85-92 
    Details
    ISSN: 1432-1912
    Keywords: Entorhinal cortex ; Isomers ; Low magnesium epilepsy ; Losigamone ; Maximal electroshock test ; Mice ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Losigamone (AO-33) is a recemate of a tetronic acid derivative. The effects of losigamone and its three isomers (AO-242, AO-294 and AO-23) were compared on maximal electroshock (MES) induced convulsions in mice and on different patterns of extracellularly recorded, low Mg 2+ induced epileptiform activity in slices of the rat temporal cortex. Lowering Mg 2+ induced recurrent short discharges in areas CA3 and CA1 while ictaform events that lasted for many seconds were induced in the entorhinal cortex. In the hippocampus the activity stayed stable over a number of hours. In contrast, the ictaform events in the entorhinal cortex changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. Afterdischarges and interictal events were absent. 50 μM AO-242 showed a similar efficacy to 50 μM AO-33 in reducing and blocking epileptiform discharges in areas CA1 and CA3 while 50 μM AO-294 and 50 μM AO-23 had weaker effects than 50 μM AO-33. Concentrations of 50 μM and 100 μM AO-242 showed a similar efficacy to AO-33 on ictaform events in the entorhinal cortex. Late recurrent discharges were also blocked by AO-33 and AO-242 although at higher concentrations (300 μM). The in vitro observations are with respect to order of efficacy in accordance with the in vivo data obtained in the maximal electroshock test in mice. The order of potency in the MES test was AO-242〉AO-33≫AO-294≫ AO-23. The results show that the erythro-isomer AO-23, although active, is much less potent than AO-33. Of the two optical isomers of losigamone the (+) isomer AO-242 is more active than the (−) form AO-294.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00175474
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of retigabine (D-23129) on different patterns of epileptiform activity induced by 4-aminopyridine in rat entorhinal cortex hippocampal slices (1999)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 359 (1999), S. 33-39 
    Details
    ISSN: 1432-1912
    Keywords: Key words Retigabine ; Anticonvulsant ; Antiepileptic ; New drug ; Field potential ; Bicuculline
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The purpose of this study was to evaluate the effects of the new anticonvulsant drug N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid ethyl ester (retigabine, D-23129, ASTA Medica, Dresden, Germany) on different patterns of epileptiform activity induced by 4-aminopyridine (4AP) in rat entorhinal cortex hippocampal slices. Application of 4AP (100 µM) induced in entorhinal cortex two different types of epileptiform activities; seizure-like events (SLE) and interictal epileptiform discharges (IED). Bicuculline (10 µM) changed 4AP-induced SLE and IED to recurrent epileptiform discharges (RED). IED were isolated after blockade of the SLE by glutamate receptor antagonists for α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, i.e. 1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX, 10 µM) and 2-amino-5-phosphonovaleric acid (APV, 30 µM). Anticonvulsant properties of retigabine were evaluated as effect on the frequency and amplitude of SLE, IED and RED. Retigabine suppressed all types of epileptiform events in a dose dependent and reversible manner. SLE were suppressed in 71.4 and 100% of slices by 5 and 10 µM, respectively. The frequency of IED was significantly reduced by 20 µM retigabine (40.9±24.5%) and IED were blocked completely by 50 µM retigabine. When IED were isolated by application of glutamate antagonists 20 µM retigabine was sufficient to block this activity completely. RED induced by combined application of bicuculline and 4AP were blocked in 71.4% of the tested slices with 100 µM retigabine. The frequency of the RED in the remaining slices was reduced by 96.1±6.1%. We conclude that retigabine acts on a large variety of different epileptiform activities in temporal lobe structures that are known to develop readily pharmacoresistant seizures.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/PL00005320
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  • 3
    Electronic Resource
    Electronic Resource
    Slow synaptic inhibition in relation to frequency habituation in dentate granule cells of rat hippocampal slices (1989)
    Springer
    Experimental brain research 78 (1989), S. 233-242 
    Details
    ISSN: 1432-1106
    Keywords: Hoppocampus ; Granule cells ; Long lasting inhibition ; Frequency habituation ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In paired pulse stimulation experiments the mechanism underlying frequency habituation of postsynaptic potentials in dentate granule cells of rat hippocampal slices was studied by measuring extra and intracellular potentials as well as changes in extracellular calcium ([Ca2+]0) and potassium concentrations ([K+]0). Orthodromic stimulation of the perforant path induced in most granule cells a late, slow hyperpolarization (SH), lasting for up to 1.2 s. During the SH the membrane conductance was increased by up to 40%. The reversal potential of the SH was around -90 mV and varied with the [K+]0. Frequency habituation was seen in all cells with the SH, whereas cells which display frequency potentiation had no SH. Lowering of [Ca2+]0 reversed paired pulse induced frequency habituation into frequency potentiation at [Ca2+]0 levels where the SH disappeared. Phaclofen blocked the SH and reversed frequency habituation into frequency potentiation. Elevating [Mg2+]0 also reversed frequency habituation into frequency potentiation and reduced the SH. We conclude that the SH represents a late, slow IPSP which is responsible for frequency habituation in dentate granule cells. We noted that during repetitive stimulation the SH soon started to fade. This effect can in part be attributed to extracellular K+-accumulation as suggested by the K+-dependence of the slow IPSP and the observations of changes in [K+]0 during repetitive stimulation. This could explain why frequency habituation reverses into frequency potentiation during repetitive stimulation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228895
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  • 4
    Electronic Resource
    Electronic Resource
    Differences in magnesium and calcium effects on N-methyl-D-aspartate- and quisqualate-induced decreases in extracellular sodium concentration in rat hippocampal slices (1988)
    Springer
    Experimental brain research 71 (1988), S. 425-430 
    Details
    ISSN: 1432-1106
    Keywords: Extracellular Na+ concentration ; Quisqualate (quis) ; N-methyl-D-aspartate (NMDA) ; Tetrodotoxin (TTX) ; Hippocampal area CA1 ; Rat ; Extracellular Ca2+ concentration ; Extracellular Mg2+ concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Decreases in extracellular sodium concentration ([Na+]o) and associated slow negative field potentials (fp's) were monitored with double barreled sodium sensitive/reference microelectrodes in area CA1 of rat hippocampal slices during iontophoretic application of the glutamate receptor agonists N-methyl-D-aspartate (NMDA) and quisqualate (quis). The effects of lowering [Ca2+]o on these signals were compared to those of lowering [Mg2+]o. Both NMDA- and quis-induced decreases in [Na+]o of up to 60 mM and in the fp's of up to 8 mV. Decreasing [Mg2+]o enhanced NMDA-induced signals, whereas quis-induced signals were unaffected. Lowering [Ca2+]o also enhanced NMDA signals, although somewhat less than lowering [Mg2+]o. This effect was still present, even when voltage dependent Na+ currents were blocked by 10-7 tetrodotoxin. Interestingly, quis-induced signals could be enhanced in a low Ca2+ medium as well, but only when high quis concentrations were used. The results suggest that, during the sorts of large decreases of [Ca2+]o observed during seizure activity, activation of NMDA receptors is facilitated.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00247502
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  • 5
    Electronic Resource
    Electronic Resource
    Influence of hypoxia on excitation and GABAergic inhibition in mature and developing rat neocortex (1993)
    Springer
    Experimental brain research 97 (1993), S. 209-224 
    Details
    ISSN: 1432-1106
    Keywords: Hypoxia ; Neocortical slice ; Synaptic transmission ; GABAergic inhibition ; Interneurons ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To analyze the functional consequences of hypoxia on the efficacy of intracortical inhibitory mechanisms mediated by gamma-aminobutyric acid (GABA), extra- and intracellular recordings were obtained from rat primary somatosensory cortex in vitro. Hypoxia, induced by transient N2 aeration, caused a decrease in stimulus-evoked inhibitory postsynaptic potentials (IPSPs), followed by a pronounced anoxic depolarization. Upon reoxygenation, the fast (f-) and long-latency (l-) IPSP showed a positive shift in the reversal potential by 24.4 and 14.9 mV, respectively. The peak conductance of the f-and l-IPSP was reversibly reduced in the postanoxic period by 72% and 94%, respectively. Extracellular field potential recordings and application of a paired-pulse inhibition protocol confirmed the enhanced sensitivity of inhibitory synaptic transmission for transient oxygen deprivation. Intracellular recordings from morphologically or electrophysiologically identified interneurons did not reveal any enhanced susceptibility for hypoxia as compared to pyramidal cells, suggesting that inhibitory neurons are not selectively impaired in their functional properties. Intracellularly recorded spontaneous IPSPs were transiently augmented in the postanoxic period, indicating that presynaptic GABA release was not suppressed. Developmental studies in adult (older than postnatal day 28), juvenile (P14–18), and young (P5-8) neocortical slices revealed a prominent functional resistance of immature tissue for hypoxia. In comparison with adult cortex, the hypoxia-induced reduction in excitatory and inhibitory synaptic transmission was significantly smaller in immature cortex. Our data indicate a hypoxia-induced distinct reduction of postsynaptic GABAergic mechanisms, leading to the manifestation of intracortical hyperexcitability as a possible functional consequence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00228690
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  • 6
    Electronic Resource
    Electronic Resource
    Effects of GABA and bicuculline on N-methyl-D-aspartate- and quisqualate-induced reductions in extracellular free calcium in area CA1 of the hippocampal slice (1986)
    Springer
    Experimental brain research 64 (1986), S. 27-36 
    Details
    ISSN: 1432-1106
    Keywords: Bicuculline ; Calcium ; GABA ; Hippocampus ; NMDA ; Quisqualate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Decreases in extracellular free calcium ([Ca2+]o) and concomitant field potentials were recorded from the dendritic and cell body layers of the CA1 field in transverse hippocampal slices. They were elicited by tetanic stimulation of Schaffer collaterals and commissural fibers or by iontophoretic application of the excitatory amino acids N-methyl-D-aspartate (NMDA) and quisqualate (Quis). Under control conditions, decreases in [Ca2+]o were found to be maximal in stratum pyramidale (SP). In stratum radiatum (SR), 100 μm away from SP, decreases in [Ca2+]o were half the size of those observed in SP. Bicuculline methiodide, bath-applied at concentrations of 10–100 μM, enhanced the reductions in [Ca2+]o, increased the field potentials in all layers and also induced “spontaneous” epileptiform activity. In the presence of bicuculline, the decreases in [Ca2+]o were particularly enhanced in SR and were often greater than those recorded in SP. This was the case for changes in [Ca2+]o induced either by repetitive electrical stimulation or by application of NMDA and Quis. When synaptic transmission was blocked by perfusing the slices with a low Ca2+ medium, all NMDA and Quis-induced changes in [Ca2+]o were predictably reduced but there was a relative enhancement of changes in [Ca2+]o in SR with respect to those in SP. We propose that, under normal conditions, an inhibitory control mediated by GABA limits the reductions of [Ca2+]o particularly in SR. In support of this proposal, we found that bath-applied GABA had a depressant action on changes in [Ca2+]o.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238198
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  • 7
    Electronic Resource
    Electronic Resource
    Extracellular calcium activity changes in cat sensorimotor cortex induced by iontophoretic application of aminoacids (1980)
    Springer
    Experimental brain research 40 (1980), S. 247-250 
    Details
    ISSN: 1432-1106
    Keywords: Extracellular Ca2+ activity ; Cerebral cortex ; Excitatory aminoacids ; Ca2+ antagonists ; GABA
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular Ca2+ activity (aCa) changes were measured with Ca2+-sensitive microelectrodes in the cat cerebral cortex during iontophoretic administration of excitatory and inhibitory aminoacids. Glutamate, aspartate and DL homcysteate usually decreased aCa from a baseline of 1.3 mM to as low as 0.1 mM. The amplitude of the changes was largest at depths between 100 and 300 μm beneath the cortical surface. The aCa decreases could be deminished or blocked by Co2+, Mn2+ or La3+ as well as by GABA. These data suggest that large Ca2+ conductances that may be voltage-sensitive are present in apical dendrites of neocortical neurones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00237788
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  • 8
    Electronic Resource
    Electronic Resource
    Stimulus-induced changes in extracellular Na+ and Cl− concentration in relation to changes in the size of the extracellular space (1982)
    Springer
    Experimental brain research 46 (1982), S. 73-84 
    Details
    ISSN: 1432-1106
    Keywords: Extracellular space ; Na+ and Cl− concentration ; Effects of metabolism on osmolarity ; Epilepsy ; Cerebral cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular Na+- and Cl−-concentrations ([Na+]o, [Cl−]o) were recorded with ion-selective microelectrodes during repetitive stimulation and stimulus-induced self-sustained neuronal afterdischarges (SAD) in the sensorimotor cortex of cats. In all cortical layers [Na+]o initially decreased by 4–7 mM. In depths of more than 600 μm below the cortical surface such decreases usually turned into increases of 2–6 mM during the course of the SADs, whereas in superficial layers [Na+]o never rose above its resting level. [Cl−]o always showed an increase in the course of the SADs often preceded by an initial small decrease. The average increase at a depth of 1,000 μm was about 7 mM. [Cl−]o reached peak values at about the end of the ictal period, whereas [Na+]o reached its maximum shortly after the end of the SAD, at times when [K+]o was still elevated above the baseline concentration. These data indicate that the extracellular osmolarity can increase during SAD by up to 30 mM. Such an increase in osmolarity can be explained by an increase in the number of intracellular particles, caused by cleavage of larger molecules during enhanced metabolism. This could lead to cell-swelling due to passive water influx from the extracellular space (ES). However, the resulting reduction of the size of the ES is calculated to be less than 10% for an increase in intracellular osmolarity by 30 mOsm. This value is too small as compared to previously measured ES-reductions under similar conditions (i.e., 30% reduction at 1,000 μm; Dietzel et al. 1980). Reductions of the size of the ES that accompany the observed changes in the ionic environment, are quantitatively explained on the basis of the extended glial buffering mechanism described in the preceding paper.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238100
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  • 9
    Electronic Resource
    Electronic Resource
    Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus-induced changes in potassium concentration (1980)
    Springer
    Experimental brain research 40 (1980), S. 432-439 
    Details
    ISSN: 1432-1106
    Keywords: Extracellular space ; K+ regulation ; Spatial K+ buffering ; Epilepsy ; Cerebral cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The time course of local changes of the extracellular space (ES) was investigated by measuring concentration changes of repeatedly injected tetramethylammonium (TMA+) and choline (Ch+) ions for which cell membranes are largely impermeable. After stimulus-induced extracellular [K+] elevations the δ[TMA+] and δ[Ch+] signals recorded with nominally K+-selective liquid ion-exchanger microelectrodes increased by up to 100%, thus indicating a reduction of the ES down to one half of its initial size. The shrinkage was maximal at sites where the K+ release into the ES was also largest. At very superficial and deep layers, however, considerable increases in extracellular K+ concentration were not accompanied by significant reductions in the ES. These findings can be explained as a consequence of K+ movement through spatially extended cell structures. Calculations based on a model combining the spatial buffer mechanism of Kuffler and Nicholls (1966) to osmolarity changes caused by selective K+ transport through primarily K+ permeable membranes support this concept. Following stimulation additional iontophoretically induced [K+]o rises were reduced in amplitude by up to 35%, even at sites where maximal decreases of the ES were observed. This emphasizes the importance of active uptake for K+ clearance out of the ES.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00236151
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  • 10
    Electronic Resource
    Electronic Resource
    Extracellular free calcium and potassium during paroxysmal activity in the cerebral cortex of the cat (1977)
    Springer
    Experimental brain research 27 (1977), S. 237-243 
    Details
    ISSN: 1432-1106
    Keywords: Ca++ selective microelectrodes ; Ca++ activity ; K+ activity ; Seizure ; Cerebral cortex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Extracellular calcium and potassium activities (aCa and aK) as well as neuronal activity were simultaneously recorded with ion-sensitive electrodes in the somatosensory cortex of cats. Baseline aCa was 1.2–1.5 mM/1, baseline a k 2.7–3.2 mM/1. Transient decreases in aCa and simultaneous increases in aK were evoked by repetitive stimulation of the contralateral forepaw, the nucleus ventroposterolateralis thalami and the cortical surface. Considerable decreases in aCa (by up to 0.7 mM/1) were found during seizure activity. A fall in aCa preceded the onset of paroxysmal discharges and the rise in aK after injection of pentylene tetrazol. The decrease in aCa led also the rise in aK during cyclical spike driving in a penicillin focus. It is concluded that alterations of Ca++ dependent mechanisms participate in the generation of epileptic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235500
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