Abstracts

Rationale: Experimental studies in the kindling model have demonstrated that the piriform cortex (PC) is involved in the initiation and spreading of seizures. PC lesional studies have demonstrated a reduction in kindling rate and prevention of secondary generalization. Additionally, low-frequency (1 Hz) deep brain stimulation (DBS) of the PC suppresses progression of amygdala kindling and expression of generalized seizures in fully kindled rats. The role of the PC in epilepsy models displaying spontaneous seizures is less explored. The aim of this study was to investigate 1) the relationship between PC lesions and seizure occurrence and generalization, and 2) the potential of PC DBS to suppress spontaneous epileptic seizures in a rat model for temporal lobe epilepsy. Methods: Eight male Sprague-Dawley rats underwent the following protocol: 1) day 0: induction of status epilepticus (SE) by intrahippocampal (IH) injection of kainic acid (KA); 2) day 4 and month 3: structural integrity determination by T2-weighted MRI; 3) month 5: implantation of bilateral recording electrodes in the dentate gyrus and a stimulation electrode in the central piriform cortex / dorsal endopiriform nucleus ipsilateral to the KA lesion (-0.8 AP, 4.9 ML, 9.0-7.75 below bregma); 4) month 6: 4 weeks of continuous video-EEG monitoring (VEM) to document seizure frequency, duration and generalization (Racine stage 1-2 versus stage 3-4-5); 5) month 7: 2 weeks of continuous high-frequency (130 Hz) Poisson-distributed PC DBS followed by a 2-week washout period. Results: In 3/8 rats T2 hyperintensities corresponding to PC oedema (MRI day 4) and lesions (MRI month 3, same rats) were found, unilaterally (rat 1 & 2) or bilaterally (rat 7). At least one spontaneous seizure was recorded in all rats during the entire 8-week VEM period. Seizure frequency, duration and generalization during the baseline period are listed in Table 1. Neither unilateral nor bilateral PC lesions were necessary for or prevented seizure occurrence; the 2 rats with unilateral PC lesions showed the highest seizure frequency. Uni- or bilateral lesions did not block seizure generalization. Although rats with PC lesions showed the highest proportion of partial seizures, the majority of seizures were generalized in all rats. Based on the results of the pilot trial (Table 2) it is unlikely (6% chance) that PC DBS strongly reduces seizure frequency or generalization in the majority of rats in the IH KA rat model for temporal lobe epilepsy. Conclusions: Neither unilateral nor bilateral PC structural integrity as judged by T2-weighted MRI is critical for seizure occurrence or generalization in the IH KA model. Our preliminary findings suggest that the central PC may not be the ideal target for DBS in this epilepsy model with spontaneous seizures.