Transcutaneous Auricular Vagus Nerve Stimulation Can Alter Autonomic Function and Induce an Antiepileptic Effect in Pentylenetetrazol- Induced Seizures in Rats

Transcutaneous auricular vagus nerve stimulation (taVNS) could be a promising treatment for epilepsy, a neurological disorder primarily characterized by seizures. One of the primary causes of premature mortality in patients with epilepsy is sudden unexpected death in epilepsy (SUDEP). Considering that reduced heart rate variability (HRV) is strongly associated with SUDEP, whether taVNS can modify the autonomic nervous system while simultaneously suppressing seizures in a rat model of epilepsy should be investigated. In this study, epileptic seizures were induced in anesthetized rats by administering pentylenetetrazol (PTZ) and performing taVNS twice. After completing the experiments, changes in HRV measurements were analyzed to investigate the function of the autonomic nervous system. From a histological perspective, the Iba-1, c-Fos, and GAD65 expression levels were examined to evaluate the antiepileptic effects of taVNS. Our study results revealed that taVNS significantly improved the HRV, including root mean square of differences between N–N intervals, standard deviation of all N–N intervals, high-frequency power, and total power. However, no significant difference was observed in the low-frequency power. Histological analysis revealed a significant reduction in Iba-1 and c-Fos expressions following taVNS, with no statistically significant difference observed in GAD65 expression. This study suggests that (1) taVNS could enhance the parasympathetic activity by improving the HRV and (2) potentially exhibit antiepileptic effects by protecting cells from damage caused by epileptic seizures.