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

Abstract

AbstractO_ST_ABSBackgroundC_ST_ABSInvasive 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. ObjectiveTo assess the effect of medial septum low-frequency deep brain stimulation to inhibit pentylenetetrazole (PTZ)-induced seizures. MethodsMale 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 {micro}A and a pulse duration of 1 ms. Rats were subjected to the experimental protocol every 24 h for seven consecutive days. ResultsSubjects 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. ConclusionsWhile this study is preclinical in nature, our findings underscore the potential of using low-frequency medial septum stimulation for future clinical applications. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/720729v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@53482org.highwire.dtl.DTLVardef@1ba5d7corg.highwire.dtl.DTLVardef@4f999aorg.highwire.dtl.DTLVardef@1ed6744_HPS_FORMAT_FIGEXP M_FIG C_FIG