Status epilepticus - Lessons and challenges from animal models

Inna Keselman, Claude G. Wasterlain, Jerome Niquet, James W.Y. Chen

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Status epilepticus (SE) is not simply a prolonged seizure. Both the clinical course and the basic mechanisms are different from a single seizure. SE often fails to respond to sequential administration of antiepileptic drugs (AEDs), originally developed for treatment of chronic seizures. Pharmacoresistance to benzodiazepines and other AEDs, which is observed soon after onset of SE, leads to loss of the effectiveness of these medications and to poor clinical outcomes. Animal models have uncovered SE-induced changes in cellular and network pathophysiology, most of them maladaptive, leading to increased excitability. Whole-cell recordings from hippocampal slices obtained from animals in SE showed alteration in both inhibitory and excitatory postsynaptic physiology. These synaptic changes result at least in part from a decrease in functional synaptic GABAA receptors (through internalization/desensitization) accompanied by a simultaneous increase in the number of membrane NMDA receptors. These findings highlight the role played by receptor trafficking in transition to and maintenance of SE. They explain, at least in part, the development of pharmacoresistance to benzodiazepines and other GABAergic drugs. These SE-associated changes suggest that the current gold standard (benzodiazepine monotherapy) treats only half the problem and that consideration should be given to using a combination of GABAA agonists and NMDA antagonists in the initial treatment.

Original languageEnglish (US)
Title of host publicationCurrent Clinical Neurology
PublisherHumana Press Inc.
Pages3-17
Number of pages15
Edition9783319495552
DOIs
StatePublished - Jan 1 2017

Publication series

NameCurrent Clinical Neurology
Number9783319495552
ISSN (Print)1559-0585

Keywords

  • Animal models
  • Brain slices
  • Electrical stimulation
  • Gamma-aminobutyric acid
  • Kainic acid
  • N-Methyl-d-aspartic acid or N-methyl-d-aspartate
  • Nerve gas
  • Pharmacoresistance
  • Pilocarpine
  • Status epilepticus

ASJC Scopus subject areas

  • Clinical Neurology

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  • Cite this

    Keselman, I., Wasterlain, C. G., Niquet, J., & Chen, J. W. Y. (2017). Status epilepticus - Lessons and challenges from animal models. In Current Clinical Neurology (9783319495552 ed., pp. 3-17). (Current Clinical Neurology; No. 9783319495552). Humana Press Inc.. https://doi.org/10.1007/978-3-319-49557-6_1