Seizure suppression by adenosine A1 receptor activation in a mouse model of pharmacoresistant epilepsy

Nicolette Gouder, Jean Marc Fritschy, Detlev Boison

Research output: Contribution to journalArticlepeer-review

153 Scopus citations

Abstract

Purpose: Because of the high incidence of pharmacoresistance in the treatment of epilepsy (20-30%), alternative treatment strategies are needed. Recently a proof-of-principle for a new therapeutic approach was established by the intraventricular delivery of adenosine released from implants of engineered cells. Adenosine-releasing implants were found to be effective in seizure suppression in a rat model of temporal lobe epilepsy. In the present study, activation of the adenosine system was applied as a possible treatment for pharmacoresistant epilepsy. Methods: A mouse model for drug-resistant mesial temporal lobe epilepsy was used, in which recurrent spontaneous seizure activity was induced by a single intrahippocampal injection of kainic acid (KA; 200 ng in 50 nl). Results: After injection of the selective adenosine A1-receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA; either 1.5 or 3 mg/kg, i.p.), epileptic discharges determined in EEG recordings were completely suppressed for a period of ≤3.5 h after the injections. Seizure suppression was maintained when 8-sulfophenyltheophylline (8-SPT), a non-brain-permeable adenosine-receptor antagonist, was coinjected systemically with CCPA. In contrast, systemic injection of carbamazepine or vehicle alone did not alter the seizure pattern. Conclusions: This study demonstrates that activation of central adenosine A1 receptors leads to the suppression of seizure activity in a mouse model of drug-resistant epilepsy. We conclude that the local delivery of adenosine into the brain is likely to be effective in the control of intractable seizures.

Original languageEnglish (US)
Pages (from-to)877-885
Number of pages9
JournalEpilepsia
Volume44
Issue number7
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Keywords

  • A receptor
  • Adenosine
  • CCPA
  • Kainic acid
  • Pharmacoresistant epilepsy

Fingerprint

Dive into the research topics of 'Seizure suppression by adenosine A<sub>1</sub> receptor activation in a mouse model of pharmacoresistant epilepsy'. Together they form a unique fingerprint.

Cite this