Deep brain stimulation suppresses epileptic seizures in rats via inhibition of adenosine kinase and activation of adenosine A1 receptors

Abstract

Aims: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus, is an effective therapy for patients with drug-resistant epilepsy, yet, its mechanism of action remains elusive. Adenosine kinase (ADK), a key negative regulator of adenosine, is a potential modulator of epileptogenesis. DBS has been shown to increase adenosine levels, which may suppress seizures via A1 receptors (A₁ Rs). We investigated whether DBS could halt disease progression and the potential involvement of adenosine mechanisms.

Methods: Control group, SE (status epilepticus) group, SE-DBS group, and SE-sham-DBS group were included in this study. One week after a pilocarpine-induced status epilepticus, rats in the SE-DBS group were treated with DBS for 4 weeks. The rats were monitored by video-EEG. ADK and A₁ Rs were tested with histochemistry and western blot, respectively.

Results: Compared with the SE group and SE-sham-DBS group, DBS could reduce the frequency of spontaneous recurrent seizures (SRS) and the number of interictal epileptic discharges. The DPCPX, an A₁ R antagonist, reversed the effect of DBS on interictal epileptic discharges. In addition, DBS inhibited the overexpression of ADK and the downregulation of A₁ Rs.

Conclusion: The findings indicate that DBS can reduce SRS in epileptic rats via inhibition of ADK and activation of A₁ Rs. A₁ Rs might be a potential target of DBS for the treatment of epilepsy.

Keywords: A1 receptors; adenosine kinase; deep brain stimulation; epilepsy.