Cellular and Molecular Events Underlying Epileptic Brain Damage a

It has been known for more than 150 years that many patients with epilepsy can have unequivocal brain damage, usually localized to the hippocampus (for literature, see Reference 1). Such findings led to several important questions. The first was whether the brain damage was secondary to the seizures, or their cause. Since it subsequently emerged that repeated seizures and/or status epilepticus can in fact cause brain damage, the next important question arose: Is the damage due to the seizure discharge per se, or to systemic complications which encroach upon the oxygenation of brain cells? A related and equally pertinent question concerns the minimal period of seizure activity that carries the risk of inducing irreversible structural and functional lesions. We must ask, Can short electroconvulsive seizures, when administered singly or repetitively, cause such lesions? Many experimental protocols have been designed to provide appropriate answers to these questions (see Reference 2). Such experiments, as well as those designed to unravel the pathophysiology of ischemic or hypoglycemic brain damage, have yielded much useful information. As a result, we can now define in some detail pathophysiological conditions under which damage is incurred, and speculate about the mechanisms involved. It is the objective of this paper to discuss the neurochemical pathology of such damage.