Effects of Vagal Stimulation on Experimentally Induced Seizures in Rats

Abstract

Repetitive stimulation of the vagus nerve inhibits chemically induced seizures in dogs. We report here the results and conclusions from studies designed to answer some of the immediate questions raised by this finding. (1) Maximal stimulation of vagal C fibers at frequencies greater than 4 Hz prevents or reduces chemically and electrically induced seizures in young male rats. (2) Antiepileptic potency is directly related to the fraction of vagal C fibers stimulated. (3) Vagal stimulation shortens but does not shut down a chemical seizure once it has begun. (4) In rats, optimal stimulus frequency is approximately 10-20 Hz; duration of stimulus, 0.5-1 ms; and stimulus strength, 0.2-0.5 mA/mm2 of nerve cross-section. These results, when taken together with similar results obtained from dogs, monkeys, and humans, strongly suggest that periodic stimulation of the vagus nerve using appropriate stimulation parameters is a powerful method for preventing seizures. The data from the literature suggest that the antiepileptic actions of vagal stimulation are largely mediated by widespread release of GABA and glycine in the brainstem and cerebral cortex. The probable pathway is via projections from the nucleus of the solitary tract to the reticular formation and thence by diffuse projections to the cortex and other areas. Intermittent vagal stimulation has the potentiality of reducing the number and/or the intensity of seizures in patients with intractable epilepsy. These results indicate that feasibility studies in humans should be continued and expanded.

Induction of c-Fos and ΔFosB Immunoreactivity in Rat Brain by Vagal Nerve Stimulation

“…Also, most of these studies were carried out using anesthetized animals and stimulation protocols with higher frequencies and duty cycles than the protocols used clinically and in the present study. Anesthesia also lowers activation of C fibers by VNS (Woodbury and Woodbury, 1990). Consequently, the effects reported in these earlier studies using anesthetized preparations may be distinct from those in unanesthetized animals.…”

“…Anesthesia can increase Fos protein throughout brain (Takayama et al, 1994), which could mask effects of vagal stimulation. Anesthesia can also change the threshold for activation of different types of fibers in the vagal bundle (Woodbury and Woodbury, 1990). Further, in all but one study (Naritoku et al, 1995), stimulation of the vagus was carried out using either electrodes or stimulation parameters that resulted in alterations of peripheral autonomic function, (eg mean arterial pressure, MAP; heart rate, HR; and/or respiratory frequency, RF).…”

Estimulación eléctrica vagal en el tratamiento de la epilepsia rebelde: Situación actual

“…Los estudios en animales no han servido únicamente para investigar el mecanismo de acción y valorar la actividad antiepiléptica, también han resultado útiles para determinar la máxima intensidad y parámetros de estimulación sin producir daño químico o eléctrico 80 . Esto es importante porque los parámetros eléctricos constituyen una variable fundamental relacionada con el control de las crisis y otros aspectos fisiológicos 40 .…”

Vagus Nerve Stimulation in the Treatment of Refractory Epilepsy

“…25 However, this finding was called into question by the observation that the clinical efficacy of VNS in humans was maintained at stimulation parameters thought not to exceed the threshold necessary for C fiber activation. 26 A subsequent study in rats observed that the VNS-induced seizure suppression remained intact, despite selective destruction of C fibers with capsaicin.…”