What was the question?
Anti-epileptic drug (AED) therapy is effective in two-thirds of individuals with epilepsy, but they are not beneficial in the remaining patients. These patients are called “refractory,” and treatment options for them include neurostimulation, dietary therapies and brain surgery.
One neurostimulation technique used in refractory epilepsy is called deep brain stimulation (DBS), a technique where electrodes are implanted and electrical impulses are delivered to specific parts of the brain. For epilepsy, DBS has been effective when a part of the brain called the anterior thalamic nucleus was stimulated. However, the reason why DBS is effective in epilepsy is not fully understood. Recently, scientists published a study in an effort to understand how DBS works. If we understand the mechanism of action underlying DBS, we can hopefully find ways to make DBS more effective for people with refractory epilepsy.
What was the hypothesis?
The scientists wanted to examine whether a compound called adenosine was responsible for efficacy of DBS. Adenosine has been shown to decrease seizures in the lab in animal models, allowing the scientists to hypothesize that DBS decreases seizure frequency by releasing adenosine.
How was the experiment conducted?
Epilepsy in the lab can be simulated in experimental animals by injecting them with drugs called chemoconvulsants. One of these drugs is pilocarpine. In this study, the scientists administered pilocarpine to rats and addressed the hypothesis in two parts:
- Rats that had epilepsy were administered DBS. To see if DBS affects electrical activity in the brain, the scientists studied epileptiform activity (the pattern of neuronal activity that is seen in epilepsy).
- The second part used microdialysis in rats that were made to have epilepsy. Microdialysis is a method by which one can measure concentrations of various compounds in the brain.
What did the scientists find?
By using a variety of experimental tools in experimental rats, the scientists found:
- Rats that were administered DBS showed less epileptiform activity (also known as ictal or seizure activity).
- Microdialysis showed that DBS indeed increased levels of adenosine.
- By using specific drugs that activate and inhibit the adenosine receptor, the scientists found that adenosine was possibly an important factor in how DBS may decrease seizure frequency.
by Sloka Iyengar, PhD
Basic Science Editor