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Epilepsy: Relationships Between Electrophysiology and Intracellular Mechanisms Involving Second Messengers and Gene Expression

Published online by Cambridge University Press:  18 September 2015

P. Gloor
P. Gloor*
Affiliation:
Department of Neurology and Neurosurgery of McGill University and the Montreal Neurological Institute
*
Montreal Neurological Institute, 3801 University St., Montreal, Quebec, Canada H3A 2B4
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Abstract:

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It is well known that pure absence epilepsy is a benign form of seizure disorder, while most others, particularly partial and convulsive seizures may have transient or permanent deleterious consequences and are more difficult to bring under therapeutic control by anticonvulsants. The hypothesis is proposed that the preservation of GABA-ergic inhibition in absence attacks and its breakdown in most other seizures may explain these differences. Breakdown of GABA-ergic inhibition allows NMDA receptors to become active. This opens the way for Ca2+ to enter the cell. Such Ca2+ entry is a long-lasting phenomenon. It is likely to be massive during most seizures except during absence attacks, and may therefore damage the neuron transiently or permanently. It may even destroy it. Ca2+ entry is also a crucial factor in the activation of the second messenger cascade which involves cytosolic as well as nuclear (genomic) components. Activation of this cascade converts short-lived electrophysiological processes occurring at the membrane into much longer-lasting intracellular processes. These may include plastic changes at the synaptic and receptor level and may account for kindling and the increasing therapy-resistance of long-standing seizure disorders. Changes resulting from massive Ca2+ entry into the neuron may explain why most seizures, except absence attacks, may have deleterious consequences of various kinds, some short-lived, some of longer duration, and some even permanent.

Type
Special Features
Information
Canadian Journal of Neurological Sciences , Volume 16 , Issue 1 , February 1989 , pp. 8 - 21
Copyright
Copyright © Canadian Neurological Sciences Federation 1989

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