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Physiological basis of pathophysiological brain rhythms


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Focal epilepsy may be induced acutely in the brain in vivo by measures which reduce inhibition or enhance excitation. Athough the various models involve different mechanisms causing the epilepsy, their epileptiform discharge patterns vary only little. Intracellular analyses in vivo and in vitro reveal that the cellular hallmark of epileptic discharge, the paroxysmal depolarization shift, is followed by a giant hyperpolarization. The latter is comprised of several, overlapping, components with different durations, including calcium dependent potassium currents and GABA dependent inhibitions. Relative reduction of one inhibitory component is compensated by other inhibitory components. In epilepsy caused by reduction of GABAergic inhibition, the absolute duration and amplitude of GABAergic inhibition may even be increased in comparison to the responses following afferent stimulation under control conditions since the excitatory drive of the paroxysmal discharges on the interneurons is strongly increased. In some interictal discharge patterns, the enhanced inhibitions within the focus determine the refractory periods of the focus. The latter is paced by neurons from the perifocal area which show a shorter inibition associated with the interictal epileptic event. The discharge pattern of the focus may switch to other patterns, either spontaneously, or as entrained by external stimulation. Such changes are caused e.g. by progressive potassium accumulations in the extracellular space with critically small intervals of the epileptic events. It is concluded that the epileptiform discharge patterns reflect intrinsic properties of the brain, and do not very well reflect the mechanism of action of the epileptogenic model. The brain is thus equipped with inherent mechanisms which favor rhythmic epileptiform discharges under certain conditions.





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O. W. Witte, Neurologische Klinik, Heinrich Heine Universitat, Moorenstr. 5, D- 40225 Dusseldorf, Germany, Email: witteo@uni-duesseldorf.de


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