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

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)-1ß, 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.

Vagal nerve stimulation attenuates IL-6 and TNFα expression in respiratory regions of the developing rat brainstem.

Pre-term infants are at greater risk for systemic infection due to an underdeveloped immune system. Airway infection results in immune up-regulation of early pro-inflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) in the brainstem. Current treatment for neonatal infection involves antibiotic administration. We previously showed that LPS injected into the trachea of neonatal rats causes changes in breathing and in IL-1ß expression in the nucleus tractus solitarii (NTS) and hypoglossal motor nucleus (XII). We hypothesize that lipopolysaccharide (LPS) instilled in the trachea also causes the up-regulation of IL-6 and TNFα in the brainstem autonomic control regions. To test this hypothesis we injected LPS into the trachea of rat pups (postnatal ages 10-12days) and then assessed changes in IL-6 and TNFα. Vagal nerve stimulation has been used in the treatment of many inflammatory disorders, including sepsis. Our experiments show that VNS attenuates the upregulation of IL-6 and TNFα caused by LPS and may be a viable alternative to antibiotics.