Seizure Suppression by Adenosine A1 Receptor Activation in a Mouse Model of Pharmacoresistant Epilepsy

Autor: Nicolette Gouder, Detlev Boison, Jean-Marc Fritschy
Rok vydání: 2003
Předmět:
Zdroj: Epilepsia. 44:877-885
ISSN: 1528-1167
0013-9580
DOI: 10.1046/j.1528-1157.2003.03603.x
Popis: Summary: 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.
Databáze: OpenAIRE
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