Rat vagus nerve stimulation model of seizure suppression: nNOS and ΔFos B changes in the brainstem

Vagus nerve stimulation (VNS) is a moderately effective treatment for intractable epilepsy. However, the mechanism of action is poorly understood. The effect of left VNS in amygdala kindled rats was investigated by studying changes in nNOS and ΔFos B expression in primary and secondary vagus nerve projection nuclei: the nucleus of the solitary tract (NTS), dorsal motor nucleus of the vagus nerve (DMV), parabrachial nucleus (PBN) and locus coeruleus (LC).Rats were fully kindled by stimulation of the amygdala. Subsequently, when the fully kindled state was reached and then maintained for ten days, rats received a single 3-min train of VNS starting 1 min prior to the kindling stimulus and lasting for 2 min afterwards. In control animals the vagus nerve was not stimulated. Animals were sacrificed 48 h later. The brainstems were stained for neuronal nitric oxide synthase (nNOS) and ΔFos B.VNS decreased seizure duration with more than 25% in 21% of rats. No VNS associated changes in nNOS immunoreactivity were observed in the NTS and no changes in ΔFos B were observed in the NTS, PBN, or LC. High nNOS immunopositive cell densities of >300 cells/mm2 were significantly more frequent in the left DMV than in the right (χ2(1) = 26.2, p < 0.01), independent of whether the vagus nerve was stimulated.We conclude that the observed nNOS immunoreactivity in the DMV suggests surgery-induced axonal damage. A 3-min train of VNS in fully kindled rats does not affect ΔFos B expression in primary and secondary projection nuclei of the vagus nerve.

► First report on this subject (cellular effects of vagus nerve stimulation on brain stem cells) in epileptic rats.
► Major effect of surgical placement of the vagus nerve electrode, independent of electrical stimulation.
► No correlation between treatment effect and nNOS/delta Fos B expression.