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

Abstract

BackgroundVagus Nerve Stimulation (VNS) is an FDA-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 cardiorespiratory 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 (IL-1β, IL-6, TNFα) and HMGB1.ResultsNeither pup viability nor number of cells labeled for pro-inflammatory cytokines in nTS nor XII was impaired by VNS. We provide evidence suggesting that chronic VNS of pregnant mothers does not impede the progress or outcome of pregnancy.ConclusionsVNS 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.

A review of vagus nerve stimulation as a therapeutic intervention

“… 45 A recent work in a rat model of VNS shows no significant effect of VNS on pups born to a dam with an implanted VNS stimulator. 46 Preliminary research suggests that VNS can be a beneficial treatment for both mother and fetus, although more research is required for a clearer picture of the outcome.…”

Vagus Nerve Stimulation Ameliorates L-NAME-induced Preeclampsia-like Symptoms in Rats Through Inhibition of the Inflammatory Response

“…The stimulation parameters are identical to those used in our previous study, 15 namely, a stimulation frequency of 5 Hz, a low voltage of 3 V, a current of 1 mA and a pulse duration of 500 µs. For the sham rats, the surgery was performed in the same way, but the cuff electrode was not implanted.…”

“…On theGDs 13,15, 17 and 19, the rats were housed separately for 24 h under the cages to collect urine samples. Urine samples were centrifuged at 2000 rpm for 15 min at 22 °C, and the supernatant was used for the analysis of protein levels by using a BCA protein assay kit (Thermo Fisher Scienti c Inc, CN, Shanghai)…”

Vagus nerve stimulation ameliorates L-NAME-induced preeclampsia-like symptoms in rats through inhibition of the inflammatory response

“…The stimulation parameters are identical to those used in our previous study, 17 namely, a stimulation frequency of 5 Hz, a low voltage of 3 V, a current of 1 mA and a pulse duration of 500 μs. For the sham rats, the surgery was performed in the same way, but the cuff electrode was not implanted.…”