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Site and mechanism of action of agents producing epilepsy in animals
Başlık:
Site and mechanism of action of agents producing epilepsy in animals
Yazar:
Lockton, John William, author.
ISBN:
9780438053151
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (225 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: Oliver Holmes.
Özet:
1. This study has attempted to identify the site within the cerebral cortex of the rat where sodium penicillin G initiates interictal epileptic spikes. A technique has been developed to overcome the problems of interpretation encountered in earlier investigations. 2. Penicillin has been applied at a number of precise cortical depths by electrophoresis from glass microelectrodes. This has allowed an assessment of the capabilities of individual cortical laminae to support drug-induced epileptiform activity. It was postulated that if there was a specific site of penicillin action then it would show a particularly high sensitivity to the convulsant action of this drug. 3. When penicillin G is applied to the cerebral cortex of the anaesthetised rat there are a number of characteristic changes in the mass electrical activity (the EEG and ECOG), of which the most stereotyped is the "interictal spike". This transient has been used to assess the degree of epileptiform activity induced. The mass electrical activity has been recorded simultaneously at a number of cortical depths - from two to four - from a battery of glass microelectrodes and has allowed the site of spike generation to be assessed. This "generator zone" was presumed to be at the level of the spike potential maximum, a parameter that was clearly delineated due to the localised nature of the spikes. In some cases the spikes were indistinguishable from the background mass activity at a level only 0.3 mm superficial or deep to that of the potential maximum. 4. The position of the generator zone with respect to the penicillin challenged depth was found to be dependent on the size of the electrophoretic current. With low currents - ones just capable of inducing interictal spikes (less than 100 nA) -the spikes were always of largest amplitude in the middle of the cortex irrespective of where the penicillin was applied. In contrast, with higher currents (150 to 300 nA) spikes were always induced which were largest at the challenged depth. In addition, the extent of the epileptiform activity induced by the two current ranges was also different, the larger one producing the greater activity both in terms of spike amplitude and spike frequency. Therefore different considerations were required in assessing the position of the sensitive zone from the two sets of experiments. 5. For low currents the onset of interictal spiking was used as a measure of the capability of a particular depth to support epileptiform activity. When equal penicillin currents were delivered at different depths in the cortex this value varied considerably between depths, from 1.5 to over 15 minutes. However, in all the experiments the middle of the cortex give the lowest values, with a sharp increase as the challenging electrode was moved superficially or deep. Moreover with these currents only the central zone between 0.4 and 0.9 mm was capable of supporting interictal activity. A theoretical analysis of the system indicated that outwith this zone the penicillin probably had to diffuse into it to induce spikes. The central zone was not however of a uniform sensitivity; there was a particular sensitive core between 0.6 and 0.8 mm. This has been shown, indirectly, to be equivalent to lower lamina III and lamina IV. The theoretical assessment of this data also indicated the requirement for a particular area of cortical tissue to support interictal activity, a "critical mass" (Reichenthal and Hochermann, 1977). 6. In contrast, for the relatively high currents, the onset of spiking could not he used "because the epileptiform activity produced persisted for long periods. All injections other than, the first in any experiment were thus given when residual spikes were occurring. To detect the effect of each penicillin injection, cumulative spike counts were plotted. Such graphs showed an increase in slope as the injected penicillin produced its effect. In control experiments, where several injections were made at the same cortical site, the latent period of this, increase was shown to be a reliable criterion for assessing lamina sensitivity. When equal penicillin currents were delivered through electrodes at different laminae in the cortex the latent period of onset of increased interictal spiking varied. The challenged lamina was identified directly by marking the positions of the recording and penicillin microelectrode tips with extracellular dyes. Thus the rank order of lamina in terms of decreasing sensitivity was : deep part of layer III-IV-II-Va-Vb. 7. The sensitive zone from both the low and high current experiments therefore coincides and is situated in lower lamina III/ lamina IV. The implications of this to epileptogenesis with reference to the postulated convulsant action of penicillin and the morphology of the cortical area under study are discussed. A removal of inhibitory GABA-ergic activity at the soma of pyramidal cells in layer III by the penicillin, allowing normal excitatory and intrinsic activity to be expressed is proposed as a possible model for the generation of the epileptiform activity observed in the present study.
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684449.1) | 684449-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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