AUTHOR=Miranda Maisa F. , Hamani Clement , de Almeida Antônio-Carlos G. , Amorim Beatriz O. , Macedo Carlos E. , Fernandes Maria José S. , Nobrega José N. , Aarão Mayra C. , Madureira Ana Paula , Rodrigues Antônio M. , Andersen Monica L. , Tufik Sergio , Mello Luiz E. , Covolan Luciene TITLE=Role of adenosine in the antiepileptic effects of deep brain stimulation JOURNAL=Frontiers in Cellular Neuroscience VOLUME=8 YEAR=2014 URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00312 DOI=10.3389/fncel.2014.00312 ISSN=1662-5102 ABSTRACT=

Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine.