title: Kindling and status epilepticus models of epilepsy: rewiring the brain.
abstract: This review focuses on the remodeling of brain circuitry associated with epilepsy, particularly in excitatory glutamate and inhibitory GABA systems, including alterations in synaptic efficacy, growth of new connections, and loss of existing connections. From recent studies on the kindling and status epilepticus models, which have been used most extensively to investigate temporal lobe epilepsy, it is now clear that the brain reorganizes itself in response to excess neural activation, such as seizure activity. The contributing factors to this reorganization include activation of glutamate receptors, second messengers, immediate early genes, transcription factors, neurotrophic factors, axon guidance molecules, protein synthesis, neurogenesis, and synaptogenesis. Some of the resulting changes may, in turn, contribute to the permanent alterations in seizure susceptibility. There is increasing evidence that neurogenesis and synaptogenesis can appear not only in the mossy fiber pathway in the hippocampus but also in other limbic structures. Neuronal loss, induced by prolonged seizure activity, may also contribute to circuit restructuring, particularly in the status epilepticus model. However, it is unlikely that any one structure, plastic system, neurotrophin, or downstream effector pathway is uniquely critical for epileptogenesis. The sensitivity of neural systems to the modulation of inhibition makes a disinhibition hypothesis compelling for both the triggering stage of the epileptic response and the long-term changes that promote the epileptic state. Loss of selective types of interneurons, alteration of GABA receptor configuration, and/or decrease in dendritic inhibition could contribute to the development of spontaneous seizures.
authors.affiliation: Department of Neuropsychiatry, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Morimoto
authors.forename: Margaret
authors.initials: M
authors.lastname: Fahnestock
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Racine
mesh_terms: D000818:Animals; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D007696:Kindling, Neurologic; D009433:Neural Inhibition; D009434:Neural Pathways / Q000503:physiopathology; D009473:Neuronal Plasticity; D013226:Status Epilepticus / Q000503:physiopathology*