Hippocampal epileptogenesis in animal models of mesial temporal lobe epilepsy with hippocampal sclerosis: The importance of the 'latent period' and other concepts

摘要

Prolonged chemoconvulsant-induced status epilepticus in rats has long been promoted as an animal model of mesial temporal lobe epilepsy with hippocampal sclerosis, under the assumption that these animals involve: (1) pathology similar to that of the human neurologic condition; (2) a seizure-free, "preepileptic" latent period of several weeks duration after injury, during which a secondary epileptogenic process gradually develops; and (3) a chronic epileptic state in which the hippocampus, in general, and the dentate gyrus, in particular, becomes a source of the spontaneous behavioral seizures that define these animals as "epileptic." Retrospective analysis suggests that all of these assumptions are in doubt. Neuropathologic studies have shown that prolonged status epilepticus causes greater extrahippocampal than hippocampal damage, and does not produce classic hippocampal sclerosis. In vivo electrophysiologic studies suggest that the hippocampus of these animals may not be "epileptic." Most importantly, studies using continuous video monitoring to detect spontaneous behavioral seizures indicate that these rats become epileptic soon after insult, before any delayed secondary processes have time to develop. High mortality, significant variability, and the lack of an extended "therapeutic window" after brain injury suggest the need to develop animal models that more closely resemble the human neurologic condition.