Abstracts

Rationale: In amygdala-kindled rats, prior studies have reported that daily transient vagus nerve stimulation (VNS) applied 2 hours prior to each amygdala stimulation had no effect on kindling development (Dedeurwaerdere et al., Neuroscience, 2006, 140 : 1443). The purpose of this study was to further determine the efficacy of VNS on epileptogenesis, testing for the first time the effect of continuous VNS instead of daily transient VNS on amygdala kindling in adult rats.Methods: Sprague-Dawley rats (n=22) were implanted with a bipolar stimulation electrode placed in the right amygdala and, one week later, with a vagus nerve (VN) cuff-electrode on the left side. The VN cuff-electrode was connected to an external stimulating device (NCP, Cyberonics Inc., Houston, TX, USA), which was immediately activated or not depending on whether rats were submitted (n=10) or not (n=12) to continuous VNS (output current : 0,25mA, pulse duration : 500 µsec, frequency : 30HZ, on/off duty cycle : 30sec/12sec) during amygdala kindling development. The kindling stimulation was started 4 days after VNS implantation and was administrated twice daily. We recorded the number of stimulations needed to reach each stages of behavioral seizures according to Racine’s classification (Electroencephalogr. Clin. Neurophysiol., 1972, 32 : 281). Rat body weight was measured before the first of the two daily kindling stimulations. Results: Continuous VNS was associated with a significant reduction in body weight gain (-16.6 ± 3.5 %, p<0.001) during the first five days following the initiation of VNS, compared with sham-stimulated animals. In rats that were not submitted to continuous VNS, the number of stimulations needed to reach each of the five consecutive behavioral seizure stage were : stage 1 : 0.8 ± 0.2 ; stage 2 : 3.1 ± 0.6 ; stage 3 : 9.2 ± 0.8 ; stage 4 : 13.7 ±0.9 ; stage 5 : 19.8 ± 0.6. VNS-treated rats exhibited a kindling progression significantly slower between stages 2 and 3 because the number of stimulations needed to reach stage 3 behavioral seizures was increased to 13.9 ± 1.0 (+51%, p<0.001), though stages 4 and 5 were reached after a comparable number of stimulations than in control rats. As a consequence of the longer time needed to reach stage 3 seizures, the cumulative after discharge duration to this stage was increased by +61 ± 25 % (p<0.01) in VNS-treated rats, as compared to control animals.Conclusions: Continuous VNS significantly delayed the early, but not late, stages of kindling development in the adult rat.