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

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.

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).

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

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.