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Epileptogenesis
About: Epileptogenesis is a research topic. Over the lifetime, 4218 publications have been published within this topic receiving 170809 citations.
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TL;DR: Results indicate that hippocampal epileptogenesis after convulsive status epilepticus is an immediate network defect coincident with neuron loss or other early changes, which is directly related and inversely proportional to the extent of neuron loss in brain regions involved in seizure initiation, spread, and clinical expression.
Abstract: Hippocampal epileptogenesis is hypothesized to involve secondary mechanisms triggered by initial brain injury. Chemoconvulsant-induced status epilepticus has been used to identify secondary epileptogenic mechanisms under the assumption that a seizure-free, pre-epileptic “latent period” exists that is long enough to accommodate delayed mechanisms. The latent period is difficult to assess experimentally because early spontaneous seizures may be caused or influenced by residual chemoconvulsant that masks the true duration of the epileptogenic process. To avoid the use of chemoconvulsants and determine the latency to hippocampal epileptogenesis and clinical epilepsy, we developed an electrical stimulation-based method to evoke hippocampal discharges in awake rats, and produce hippocampal injury and hippocampal-onset epilepsy reliably. Continuous video-monitoring and granule cell layer recording determined whether hippocampal epileptogenesis develops immediately or long after injury. Bilateral perforant pathway stimulation for 3 hr evoked granule cell epileptiform discharges and convulsive status epilepticus with minimal lethality. Spontaneous Stage 3−5 behavioral seizures reliably developed within 3 days post-stimulation, and all 72 spontaneous behavioral seizures recorded in 10 animals were preceded by spontaneous granule cell epileptiform discharges. Histological analysis confirmed a reproducible pattern of limited hippocampal and extra-hippocampal injury, including an extensive bilateral loss of hilar neurons throughout the hippocampal longitudinal axis. These results indicate that hippocampal epileptogenesis after convulsive status epilepticus is an immediate network defect coincident with neuron loss or other early changes. We hypothesize that the latent period is directly related and inversely proportional to the extent of neuron loss in brain regions involved in seizure initiation, spread, and clinical expression.
78 citations
TL;DR: In epilepsy research, animal models are used to evaluate the possible specific efficacies of the compound against different types of seizures or epilepsy, and to characterize the preclinical efficacy of novel compounds during chronic administration.
Abstract: In epilepsy research, animal models serve a variety of purposes. First, they are used in the search for new antiepileptic drugs. Second, once the anticonvulsant activity of a novel compound has been detected, animal models are used to evaluate the possible specific efficacies of the compound against different types of seizures or epilepsy. Third, animal models can be used to characterize the preclinical efficacy of novel compounds during chronic administration. Such chronic studies can serve different objectives, for instance, evaluation of whether drug efficacy changes during prolonged treatment, e.g. because of the development of tolerance, or examination of whether a drug exerts antiepilep-togenic effects during prolonged administration, i.e. is a true antiepileptic drug. Fourth, animal models are employed to characterize the mechanism of action of old and new antiepileptic drugs. Fifth, certain models can be used to study mechanisms of drug resistance in epilepsy. Sixth, in view of the possibility that chronic brain dysfunction, such as epilepsy, might lead to altered sensitivity to drug adverse effects, models involving epileptic animals are useful to study whether epileptogenesis alters the adverse effect potential of a given drug. Seventh, animal models are needed for studies on the pathophysiology of epilepsies and epileptic seizures, e.g. the processes involved in epileptogenesis and ictogenesis (Lothman 1996a).
78 citations
TL;DR: It is shown by whole cell recording that carbamazepine, in contrast to phenytoin, blocks N-methyl-D-aspartate (NMDA)-activated membrane currents in cultured neurons in a dose-dependent fashion.
Abstract: The antiepileptic agents, carbamazepine and phenytoin, suppress seizures in man and convulsant-induced hyperactivity in spinal cord nerve cell cultures. In the present study, we have shown by whole cell recording that carbamazepine, in contrast to phenytoin, blocks N-methyl-D-aspartate (NMDA)-activated membrane currents in cultured neurons in a dose-dependent fashion. The NMDA receptor-activated channel, which is blocked at physiological concentrations of Mg2+ at resting membrane potential, can be activated by glutamate in depolarized neurons and thus be involved in epileptogenesis. Therefore, the block of NMDA-evoked membrane currents in cultured neurons may contribute to the clinical effectiveness of carbamazepine.
78 citations
TL;DR: Recent therapeutic strategies to treat epilepsy with neuropeptides, which are based on viral vector technology, are highlighted, and how such interventions need to be refined in order to address human disease is outlined.
78 citations
TL;DR: It is demonstrated that status epilepticus causes a unique and selective reorganization of the CB1 receptor system that persists as a permanent hippocampal neuronal plasticity change associated with the development of acquired epilepsy.
78 citations