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Role of adenosine in the antiepileptic effects of deep brain stimulation

2014; Frontiers Media; Volume: 8; Linguagem: Inglês

10.3389/fncel.2014.00312

1662-5102

Maísa Ferreira Miranda, Clement Hamani, Antà ́nio-Carlos G. de Almeida, Beatriz Oliveira Amorim, Carlos Eduardo Macedo, Maria José da Silva Fernandes, José N. Nobrega, Mayra C. Aarão, Ana Paula Madureira, Antà ́nio M. Rodrigues, Mônica L. Andersen, Sérgio Tufik, Luiz E. Mello, Luciene Covolan,

Adenosine and Purinergic Signaling

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 five 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 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.