Effect of Vagus Nerve Stimulation on the GASH/Sal Audiogenic-Seizure-Prone Hamster

Abstract

[ES] El hamster epiléptico "GASH/Sal" (Genetic Audiogenic Seizures Hamster / Salamanca) es el resultado de una mutación espontánea natural y constituye un modelo animal ideal de epilepsia refleja, ya que ante un sonido de unos determinados parámetros responde siempre con crisis. Decidimos profundizar en el conocimiento de la estimulación del nervio vago en este modelo. Nuestro trabajo demuestra la efectividad de la terapia crónica o a largo plazo mediante el empleo de dispositivos plenamente implantables, probando los dispositivos comerciales existentes y con el desarrollo de un generador adecuado al tamaño del hamster. El mecanismo de acción está mediado por el descenso de mediadores inflamatorios.

[EN] Vagus nerve stimulation (VNS) is an adjuvant neuromodulation therapy for the treatment of refractory epilepsy. However, the mechanisms behind its effectiveness are not fully understood. Our aim was to develop a VNS protocol for the Genetic Audiogenic Seizure Hamster from Salamanca (GASH/Sal) in order to evaluate the mechanisms of action of the therapy. The rodents were subject to VNS for 14 days using clinical stimulation parameters by implanting a clinically available neurostimulation device or our own prototype for laboratory animals. The neuroethological assessment of seizures and general behavior were performed before surgery, and after 7, 10, and 14 days of VNS. Moreover, potential side effects were examined. Finally, the expression of 23 inflammatory markers in plasma and the left-brain hemisphere was evaluated. VNS significantly reduced seizure severity in GASH/Sal without side effects. No differences were observed between the neurostimulation devices. GASH/Sal treated with VNS showed statistically significant reduced levels of interleukin IL-1β, monocyte chemoattractant protein MCP-1, matrix metalloproteinases (MMP-2, MMP-3), and tumor necrosis factor TNF-α in the brain. The described experimental design allows for the study of VNS effects and mechanisms of action using an implantable device. This was achieved in a model of convulsive seizures in which VNS is effective and shows an anti-inflammatory effect.