The course of cellular alterations associated with the development of spontaneous seizures after status epilepticus.
Chronic epilepsy, as a consequence of status epilepticus, has been studied in animal models in order to analyze the cellular mechanisms responsible for the subsequent occurrence of spontaneous seizures. Status epilepticus, induced by either kainic acid or pilocarpine or by prolonged electrical stimulation, causes a characteristic pattern of neuronal death in the hippocampus; which is followed--after an apparent latent period--by the development of chronic, recurrent, spontaneous seizures. The question most relevant to this conference is the degree to which the subsequent chronic seizures contribute further to epileptogenesis and brain damage. This article addresses the temporal and anatomical parameters that must be understood in order to address this question. (1) How does one evaluate experimentally whether the chronic epileptic seizures that follow status epilepticus contribute to epileptogenesis and lead to brain damage? To answer this question, we must first know the time course of the development of the chronic epileptic seizures, and whether the interval between subsequent individual chronic seizures is a relevant factor. (2) What anatomical parameters are most relevant to the progression of epilepsy? For instance, how does loss of inhibitory interneurons potentially influence seizure generation and the progressive development of epileptogenesis? Does axon sprouting and formation of new synaptic connections represent a form of seizure-induced brain damage? These specific issues bear directly on the general question of whether seizures damage the brain during the chronic epilepsy that follows status epilepticus.
Dudek
F Edward
FE
Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, CO 80523, USA. ed.dudek@colostate.edu
Hellier
Jennifer L
JL
Williams
Philip A
PA
Ferraro
Damien J
DJ
Staley
Kevin J
KJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D012640:Seizures / Q000473:pathology / Q000503:physiopathology*; D013226:Status Epilepticus / Q000473:pathology / Q000503:physiopathology*
D018690:Excitatory Amino Acid Agonists; D007608:Kainic Acid