Vagus nerve stimulation in pregnant rats and effects on inflammatory markers in the brainstem of neonates

Abstract

BackgroundVagus nerve stimulation (VNS) is an Food and Drug Administration-approved method delivering electrical impulses for treatment of depression and epilepsy in adults. The vagus nerve innervates the majority of visceral organs and cervix, but potential impacts of VNS on the progress of pregnancy and the fetus are not well studied.MethodsWe tested the hypothesis that VNS in pregnant dams does not induce inflammatory changes in the cardio-respiratory control regions of the pups' brainstem, potentially impacting the morbidity and mortality of offspring. Pregnant dams were implanted with stimulators providing intermittent low or high frequency electrical stimulation of the sub-diaphragmatic esophageal segment of the vagus nerve for 6-7 days until delivery. After birth, we collected pup brainstems that included cardio-respiratory control regions and counted the cells labeled for pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor-α) and high mobility group box 1.ResultsNeither pup viability nor number of cells labeled for pro-inflammatory cytokines in nucleus tractus solitarii or hypoglossal motor nucleus was impaired by VNS. We provide evidence suggesting that chronic VNS of pregnant mothers does not impede the progress or outcome of pregnancy.ConclusionVNS does not cause preterm birth, affect well-being of progeny, or impact central inflammatory processes that are critical for normal cardiovascular and respiratory function in newborns.