Early treatment suppresses the development of spike-wave epilepsy in a rat model. Journal Articles uri icon

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abstract

  • PURPOSE: Current treatments for epilepsy may control seizures, but have no known effects on the underlying disease. We sought to determine whether early treatment in a model of genetic epilepsy would reduce the severity of the epilepsy phenotype in adulthood. METHODS: We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij) rats, an established model of human absence epilepsy. Oral ethosuximide was given from age p21 to 5 months, covering the usual period in which seizures develop in this model (age approximately 3 months). Two experiments were performed: (1) cortical expression of ion channels Nav1.1, Nav1.6, and HCN1 (previously shown to be dysregulated in WAG/Rij) measured by immunocytochemistry in adult treated rats; and (2) electroencephalogram (EEG) recordings to measure seizure severity at serial time points after stopping the treatment. RESULTS: Early treatment with ethosuximide blocked changes in the expression of ion channels Nav1.1, Nav1.6, and HCN1 normally associated with epilepsy in this model. In addition, the treatment led to a persistent suppression of seizures, even after therapy was discontinued. Thus, animals treated with ethosuximide from age p21 to 5 months still had a marked suppression of seizures at age 8 months. DISCUSSION: These findings suggest that early treatment during development may provide a new strategy for preventing epilepsy in susceptible individuals. If confirmed with other drugs and epilepsy paradigms, the availability of a model in which epileptogenesis can be controlled has important implications both for future basic studies, and human therapeutic trials.

authors

  • Blumenfeld, Hal
  • Klein, Joshua P
  • Schridde, Ulrich
  • Vestal, Matthew
  • Rice, Timothy
  • Khera, Davender S
  • Bashyal, Chhitij
  • Giblin, Kathryn
  • Paul-Laughinghouse, Crystal
  • Wang, Frederick
  • Phadke, Anuradha
  • Mission, John
  • Agarwal, Ravi K
  • Englot, Dario J
  • Motelow, Joshua
  • Nersesyan, Hrachya
  • Waxman, Stephen G
  • Levin, April R

publication date

  • March 2008

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