Abstracts

Rationale: The piriform cortex (PC) is said to play a role in the genesis and propagation of epileptic seizures (Piredda & Gale, 1985). Olfactory stimulation is suggested to have a suppressive effect on seizures as it was found to reduce the seizure susceptibility in amygdala-kindled rats (Ebert & Löscher, 2000) and seizure severity in hippocampus-kindled ones (Valentine, Fremit, & Teskey, 2005). Furthermore, electrical stimulation of the PC delayed seizure development in the kindling model (Yang et al., 2006) and abolished severe seizures in the kainic acid (KA) model (Bayat et al., 2017). Given the inhibitory effect of piriform stimulation on seizure development, we investigated the effects of olfactory stimulation during kainate-induced status epilepticus (SE).    Methods: Seventeen adult male Sprague-Dawley rats were implanted with recording electrodes in the left anterior PC and bilateral hippocampi. Olfactory stimulation during KA injection was done with distilled water on control rats (n=8) and ammonia on experimental rats (n=9). Animals were injected with KA every hour until they developed 8-10 severe seizures on the Racine scale within an hour. During SE induction, animals were exposed to either distilled water or ammonia for a duration of 20 sec every 5 minutes. Olfactory stimulation began 20 minutes prior to the first injection and stopped once the animals attained SE. EEGs were reviewed and counted for seizures.  Results: We found no effect of olfactory stimulation on the frequency (p= 0.41), duration (p= 0.96), or severity (p=0.77) of seizures between the control and experimental groups. Furthermore, the time to reach the first seizure after the first KA injection was not different between the two groups (p=1.0). As regards long-term outcome, 4/8 animals in the control group progressed to having spontaneous recurrent seizures compared with 4/9 in the ammonia group (p= 0.57). Conclusions: Our findings suggest that olfactory stimulation by ammonia at a frequency of 20 sec every 5 minutes does not have a suppressive effect on kainate-induced SE seizures. Future projects will establish whether different olfactory stimuli may have anti-seizure effects, and whether olfactory stimulation can reduce spontaneous recurrent seizures. Funding: This study was made possible by the startup funds from The George Washington University for MZK. There are no other conflicts of interest related to this work. References:Bayat, A., Skopin, M. D., Joshi, S., Siddu, M., Mukharesh, L., Jahan, S., … Koubeissi, M. Z. (2017). Effects of low-frequency electrical stimulation of the anterior piriform cortex on kainate-induced seizures in rats. Epilepsy & Behavior: E&B, 72, 1–7. https://doi.org/10.1016/j.yebeh.2017.04.002Ebert, U., & Löscher, W. (2000). Strong olfactory stimulation reduces seizure susceptibility in amygdala-kindled rats. Neuroscience Letters, 287(3), 199–202.Piredda, S., & Gale, K. (1985). A crucial epileptogenic site in the deep prepiriform cortex. Nature, 317(6038), 623–625.Valentine, P. A., Fremit, S. L., & Teskey, G. C. (2005). Sensory stimulation reduces seizure severity but not afterdischarge duration of partial seizures kindled in the hippocampus at threshold intensities. Neuroscience Letters, 388(1), 33–38. https://doi.org/10.1016/j.neulet.2005.06.028Yang, L.-X., Jin, C.-L., Zhu-Ge, Z.-B., Wang, S., Wei, E.-Q., Bruce, I. C., & Chen, Z. (2006). Unilateral low-frequency stimulation of central piriform cortex delays seizure development induced by amygdaloid kindling in rats. Neuroscience, 138(4), 1089–1096. https://doi.org/10.1016/j.neuroscience.2005.12.006