Evoked Potentials in Neocortical Focal Epileptogenesis in the Rat

Bashir, Zafar Iqbal (1988) Evoked Potentials in Neocortical Focal Epileptogenesis in the Rat. PhD thesis, University of Glasgow.

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The aims of this work were to investigate some of the mechanisms underlying the development of epileptiform activity by studying the changes in evoked potential characteristics that occurred in the in vivo penicillin model of focal epilepsy and to use any such findings as a means of further investigation into the role of the different excitatory receptors in this abnormal activity. Experiments were performed on 93 male wistar rats anaesthetised with urethane (1.9 g/kg; intraperitoneally) . The electrocorticogram (ECoG) and intracortical activity was continually monitored whilst penicillin was electrophoretically ejected into the neocortex in order to produce epileptiform activity. Investigations into the mechanisms of epileptiform activity, using both in-vitro and in-vivo models of focal epilepsy, have on the whole, concentrated on the established focus and the characteristics of established epileptic activity, whether in the form of the extracellularly recorded epileptic spike or the intracellularly recorded paroxysmal depolarisation shift. (PDS). A disadvantage of such an approach is that it cannot yield any information as to any changes in cortical activity that may be occurring before the appearance of the established epileptic focus; although the processes underlying the gross manifestations of epilepsy can be studied, those that lead to such a state cannot. In this study I have used evoked cortical activity to follow any changes that may be occurring in cortical activity before spontaneous epileptiform activity occurs. Evoked potentials can provide an indication as to the overall state of cortical excitability; any changes in cortical excitability being reflected by appropriate changes in evoked activity. During the development of the acute penicillin epileptiform focus in the rat neocortex two distinct and separable stages were defined by the investigation of the changing characteristics of somatosensory evoked potentials (SEPs) and potentials evoked by direct cortical stimulation (DCS) . The first indication that two separate phases of cortical hyperexcitability might exist arose from the differences between the waveforms of enhanced evoked potentials during the development of the epileptiform focus. Small concentrations of penicillin (ejected by electrophoretic currents less than -100 nA) resulted in the enhancement of the amplitude of evoked potentials (up to three times pre-drug levels) with no change in the waveform (phase I); the enhanced potentials were very similar in appearance to normal evoked potentials. Phase I usually occurred within five to ten minutes after the start of penicillin ejection and occurred before the onset of spontaneous epileptiform spiking. Larger concentrations of penicillin (ejected by electrophoretic currents greater than -150 nA) resulted in an enhancement of duration (up to three times the pre-drug levels) as well as further increases in the amplitude (up to nine times pre-drug levels) of evoked potentials (phase II). Phase II was associated with the onset of spontaneous epileptiform spikes, which were very similar in appearance to the enhanced evoked potentials in phase II. The concept of two phases in penicillin epileptogenesis was further substantiated by the findings that the refractory period of the potentials enhanced by small doses of penicillin (phase I) was the same as the refractory period of normal potentials (less than 100 ms for SEPs and 40 ms for DEPs). However the refractory period of enhanced evoked potentials in phase II was much greater (in excess of 300 ms) than that of both normal potentials and evoked potentials in phase II. The stimulus strength response relationship of normal evoked potentials and evoked potentials in phase I were very similar to one another and both followed a sigmoidal relationship. (Abstract shortened by ProQuest.).

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Physiology, Neurosciences
Date of Award: 1988
Depositing User: Enlighten Team
Unique ID: glathesis:1988-77793
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jan 2020 11:53
Last Modified: 14 Jan 2020 11:53
URI: https://theses.gla.ac.uk/id/eprint/77793

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