Experimental Models of Status Epilepticus and Neuronal Injury for Evaluation of Therapeutic Interventions
Top Cited Papers
Open Access
- 5 September 2013
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 14 (9), 18284-18318
- https://doi.org/10.3390/ijms140918284
Abstract
This article describes current experimental models of status epilepticus (SE) and neuronal injury for use in the screening of new therapeutic agents. Epilepsy is a common neurological disorder characterized by recurrent unprovoked seizures. SE is an emergency condition associated with continuous seizures lasting more than 30 min. It causes significant mortality and morbidity. SE can cause devastating damage to the brain leading to cognitive impairment and increased risk of epilepsy. Benzodiazepines are the first-line drugs for the treatment of SE, however, many people exhibit partial or complete resistance due to a breakdown of GABA inhibition. Therefore, new drugs with neuroprotective effects against the SE-induced neuronal injury and degeneration are desirable. Animal models are used to study the pathophysiology of SE and for the discovery of newer anticonvulsants. In SE paradigms, seizures are induced in rodents by chemical agents or by electrical stimulation of brain structures. Electrical stimulation includes perforant path and self-sustaining stimulation models. Pharmacological models include kainic acid, pilocarpine, flurothyl, organophosphates and other convulsants that induce SE in rodents. Neuronal injury occurs within the initial SE episode, and animals exhibit cognitive dysfunction and spontaneous seizures several weeks after this precipitating event. Current SE models have potential applications but have some limitations. In general, the experimental SE model should be analogous to the human seizure state and it should share very similar neuropathological mechanisms. The pilocarpine and diisopropylfluorophosphate models are associated with prolonged, diazepam-insensitive seizures and neurodegeneration and therefore represent paradigms of refractory SE. Novel mechanism-based or clinically relevant models are essential to identify new therapies for SE and neuroprotective interventions.This publication has 138 references indexed in Scilit:
- Spatiotemporal pattern of neuronal injury induced by DFP in rats: A model for delayed neuronal cell death following acute OP intoxicationToxicology and Applied Pharmacology, 2011
- Disease-modifying activity of progesterone in the hippocampus kindling model of epileptogenesisNeuropharmacology, 2010
- Curing epilepsy: Progress and future directionsEpilepsy & Behavior, 2009
- Microfluidics and multielectrode array-compatible organotypic slice culture methodJournal of Neuroscience Methods, 2009
- Hippocampal neurogenesis and neural stem cells in temporal lobe epilepsyEpilepsy & Behavior, 2009
- Neurosteroids reduce inflammation after TBI through CD55 inductionNeuroscience Letters, 2007
- Effects of chronic neonatal nicotine exposure on nicotinic acetylcholine receptor binding, cell death and morphology in hippocampus and cerebellumNeuroscience, 2007
- Adult epilepsyThe Lancet, 2006
- ORGANOTYPIC CULTURES OF NEURAL TISSUETrends in Neurosciences, 1988
- Seizures produced by pilocarpine: Neuropathological sequelae and activity of glutamate decarboxylase in the rat forebrainBrain Research, 1986