Excitatory Transmitters and Epilepsy-Related Brain Damage

Abstract

Publisher Summary Either systemic or intraamygdaloid administration of cholinergic agonists or cholinesterase inhibitors results in sustained seizure activity and a pattern of acute brain damage resembling what is known to occur in human epilepsy. It is observed that a similar pattern of brain damage occurs because of sustained seizures induced by any of several methods and in each case, the cytopathological changes resemble the excitotoxin type of cellular damage induced by glutamate or aspartate. The chapter discusses kainic acid as an enigmatic excitotoxin. The chapter also discusses some experiments to clarify the possible involvement of specific transmitter systems in seizure-related brain damage phenomena. Since it has been demonstrated that a specific type of cytopathological reaction-namely an excitotoxic type of reaction-results from sustained seizures regardless of the inductory method employed, this type of reaction can reasonably be interpreted as a seizure-mediated phenomenon. Concerning the role of cholinergic mechanisms either in experimental or human seizure-related brain damage syndromes, it is a possibility that cholinergic circuits contribute to the pathophysiology in a manner that glutamate/aspartate circuits cannot. It means that if excessive synaptic release of glutamate or aspartate progresses rapidly to depolarization block, circuits employing these transmitters are an unlikely source of the sustained drive that keeps neurons firing for hours in status epilepticus.