A new rat model of seizures suitable for screening antiepileptic electrical stimulation therapies

Cristian Sevcencu, Jianhang Jiao, Kristian Rauhe Harreby, Winnie Jensen

Research output: Contribution to journalJournal articleResearchpeer-review

1 Citation (Scopus)

Abstract

The antiepileptic effects of the electrical stimulation therapies developed for patients with intractable epilepsies depend critically on the stimulation parameters, including the pulse duration, current, and frequency. Consequently, optimization of such therapies requires many animals for testing each of the stimulation parameters alone or in combination, which is costly and time consuming. This drawback could be reduced by testing several stimulation paradigms in each animal, but this requires an animal model of long-lasting seizures allowing such repetitive tests. This study was performed to validate such a model of long-lasting seizures. The present analysis was performed on electrocorticogram and intracortical signals collected from the somatosensory cortex of 11 Sprague Dawley rats. A protocol of controlled intravenous infusion of pentylenetetrazol (PTZ) was developed to induce spike-and-wave (SW) seizures and maintain stable those seizures for the whole experimental time. SW discharges were induced and maintained stable for 2 h in all rats through a two-stage infusion of PTZ. During the first stage, the SW discharges were induced by 2.5 min infusion of 10 mg/kg/min PTZ. During the second stage, the SW discharges were maintained at a stable level of frequency and power for 2 h via a 0.21 mg/kg/min PTZ infusion rate. The proposed animal model of seizures is characterized by SW discharges which remain stable for 2 h. This 2-h long time interval allows repetitive tests with different stimulation parameters in each animal, which may lead to a significant reduction of the number of animals necessary for optimizing electrical stimulation therapies developed to inhibit seizures.

Original languageEnglish
JournalArtificial Organs
Volume42
Issue number1
Pages (from-to)94-99
Number of pages6
ISSN0160-564X
DOIs
Publication statusPublished - Jan 2018

Keywords

  • Journal Article
  • —Model
  • Pentylenetetrazol
  • —Seizures
  • —Spike-and-wave
  • Pentylenetetrazole/administration & dosage
  • Seizures/chemically induced
  • Humans
  • Rats
  • Somatosensory Cortex/physiopathology
  • Male
  • Electrocorticography/instrumentation
  • Rats, Sprague-Dawley
  • Convulsants/administration & dosage
  • Electrodes
  • Animals
  • Time Factors
  • Electric Stimulation Therapy/instrumentation
  • Infusions, Intravenous
  • Disease Models, Animal

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