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Acta Physiologica 2009; Volume 195, Supplement 670
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Spring Meeting 2009
3/7/2009-3/7/2009
Ghent University, Gent, Belgium
ANTI-EPILEPTIC EFFECTS OF VAGUS NERVE STIMULATION IN THE FOCAL PILOCARPINE MODEL
Abstract number: P-10
Mollet1 L., Clinckers2 R., Raedt1 R., Meurs1 A., Wyckhuys1 T., Van Dycke1 A., El Tahry1 R., Vonck1 K., Wadman3 W., Michotte2 Y., Smolders2 I., Boon1 P.
1Laboratory for Clinical and Experimental Neurophysiology, Department of Neurology, Ghent University Hospital, Belgium
2Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Belgium
3Swammerdam Institute of Life Sciences, Department of Neurobiology, University of Amsterdam, Amsterdam, The Netherlands
Purpose:
Although vagus nerve stimulation (VNS) is an approved treatment for patients with refractory epilepsy, its mechanism of action is still unclear. Enhancement of noradrenalin release in the hippocampus, caused by altered activity in the locus coeruleus, might contribute to the anti-convulsive effect of VNS. The aim of this study was to evaluate the effects of VNS on pilocarpine-induced limbic seizures and on hippocampal extracellular neurotransmitter concentrations in vivo in rats.
Methods:
Rats (n=14) were implanted with a stimulation electrode around the left vagal nerve. Depth EEG electrodes and a microdialysis probe were stereotactically inserted into the left hippocampus. One week after surgery EEG recording and microdialysis was started. Two hours after the start of the experiment VNS was initiated in half of the rats and continued until the end of the experiment. Two hours after VNS initiation, limbic seizures were evoked in both the control and stimulated group by intrahippocampal administration of pilocarpine via the microdialysis probe. Behavioral changes indicative of seizure activity and hippocampal EEG were monitored. Concentration of noradrenalin, dopamine, serotonin and GABA were measured.
Results:
In the stimulated group, the scores of behavioral seizures were significantly (p<0.01) reduced compared to control (median 3 vs. 12 in the control group). VNS did not attenuate the latency to pilocarpine-induced limbic seizures but significantly reduced the duration of the seizures (54 37 min vs. 101 23 min in the control group). Moreover, VNS resulted in a significant increase in hippocampal extracellular noradrenalin, but had no effect on dopamine, serotonin and GABA levels.
Conclusion:
Vagus nerve stimulation (VNS) induces a rapid increase in hippocampal extracellular noradrenalin concentration and a reduction in behavioral scores and duration of pilocarpine-induced limbic seizures. It needs to be investigated whether there is a causal relationship between the increased noradrenalin concentration and the anticonvulsant effect of VNS.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 670 :P-10