Effects of medial septum low-frequency deep brain stimulation on pentylenetetrazol-induced seizures in rats

Abstract Background Invasive neuromodulation may be used in patients if seizure medications fail and surgery is not an option. However, moderate success is achieved and improved paradigms are required. The medial septum has been considered a suitable target for the treatment of temporal lobe epilepsy due to its location and connectivity. Objective To assess the effect of medial septum low-frequency deep brain stimulation to inhibit pentylenetetrazole (PTZ)-induced seizures. Methods Male Sprague-Dawley rats were stereotaxically implanted in the medial septum and left dorsal hippocampus one week prior to the experimental protocols. Then, the animals were assigned to three experimental groups: 1) 10 Hz + PTZ (n=3); 2) 5 Hz + PTZ (n=7); and 3) 5 Hz (n=7). The stimulation consisted of a 30 min train of biphasic square-wave pulses at a current of 150 µA and a pulse duration of 1 ms. Rats were subjected to the experimental protocol every 24 h for seven consecutive days. Results Subjects exposed to the 10 Hz died after the first PTZ injection. The 5 Hz stimulation not only prevented the animals’ death, but also induced a protective effect against generalization. Surprisingly, in both 5 Hz groups, septal and hippocampal spike-wave-like discharges were detected (mainly integrated by theta oscillations). This phenomenon was correlated with the generalization avoidance. Conclusions While this study is preclinical in nature, our findings underscore the potential of using low-frequency medial septum stimulation for future clinical applications. Graphical Abstract