Abstracts

Vagus nerve stimulation (VNS) is a neurophysiological adjunctive treatment for refractory epilepsy. A positive effect of VNS has been shown in a great number of human and animal studies, however the precise mechanism of action is not known. Through diffuse projections of the vagus nerve in the nervous system, VNS can have a broad effect on neuronal excitability. Micro-PET (positron emission tomography) is used for quantitative determination of the location of positron emitting isotopes in the tissue of small animals. This technique permits the monitoring of biochemical processes over time both during a scan and across multiple scans of the same subject. The aim of this study was to explore the effect of acute and chronic VNS on glucose metabolism in Wistar rats, using 2-[¹⁸F]-fluoro-2-deoxy-D-glucose (FDG) as a tracer. Male Wistar rats (300-350g) were implanted with a cuff-electrode around the left vagus nerve. During a 2-week period three scans were taken 45 min after [¹⁸F]-FDG (0.2 mCi, i.v.) injection. During the baseline period (day 1-7), the animals (n= 8) were not stimulated and a baseline scan was taken on day 7. In the second week (day 8-14), five animals were stimulated 24 hours-a-day with the following stimulation parameters: output current: 1.5 mA, frequency: 30 Hz, pulse width: 500 [micro]s, on/off time: 60 s/ 12 s. Three control animals were not stimulated. To investigate the acute effect, a scan of the control group (n= 3) and VNS group (n= 4) was taken on day 8, when VNS was activated. As to the chronic effect, a scan was taken after one week of stimulation on day 14 in both control (n= 3) and VNS group (n= 3). MRI-data of the rat brain were used to assign regions of interest (ROI): cortex, limbic structures, cerebellum and brainstem. After acquisition, the images of the PET and MRI-scan were manually fused. Left/right ratios of the ROI were compared between the control and VNS group and between the different points of time (day 7, 8 and 14). There was no change in left/right ratio in the different brain regions after acute VNS. A trend towards an increase in left/right ratio in the limbic structures after chronic VNS was found. Limbic structures play an important role in epilepsy and also human imaging studies show evidence of the involvement of the limbic system in the action of VNS. This study shows a trend towards an increased left/right ratio in the limbic structures of the rat brain due to chronic VNS, but this study still needs to be refined and extended. (Supported by BOF Grants 011D9601 and 011105399, FWO grants 1.5236.99 and 6.0324.02, and by the Clinical Epilepsy Grant Ghent University Hospital 2000-2004.)