Role of adenosine in the antiepileptic effects of deep brain stimulation

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.

Purinergic Signalling and Neurological Diseases: An Update

“…P2Y12 knockout mice exhibited reduced seizure-induced increases in microglial process numbers and worsened kainate-induced seizure behaviours [85]. It has been suggested that the antiepileptic effects of deep brain stimulation may be mediated by adenosine [86]. Experiments support a role for post-transcriptional regulation of the P2X7 receptors and it was suggested that therapeutic targeting of microRNA-22 may prevent inflammation and development of epilepsy [87].…”

Long-Term Effects of Anterior Thalamic Nucleus Deep Brain Stimulation on Spatial Learning in the Pilocarpine Model of Temporal Lobe Epilepsy

“…Previous studies using the pilocarpine model have shown that anterior thalamic nucleus (ANT) DBS reduced the latency to seizures and SE onset (5,(12)(13)(14)(15). In chronic pilocarpine epileptic rats, ANT stimulation reduced hippocampal excitability and seizure rate (12).…”

The effect of fornix deep brain stimulation in brain diseases

“…In addition to the local electrical effects of DBS, researchers found that DBS could also induce neurochemical changes locally and through the stimulated network. For instance, DBS of the anterior thalamus for the treatment of epilepsy in a rodent model induces the release of hippocampal adenosine [39]. Moreover, DBS has shown to induce plastic changes with regard to synaptic plasticity and neurogenesis.…”