The vagus nerve regulates immunometabolic homeostasis in the ovine fetus near term: impact on terminal ileum
The contribution of the vagus nerve to inflammation and glucosensing in the fetus is not understood. We hypothesized that vagotomy (Vx) will trigger a rise in systemic glucose levels and this will be enhanced during systemic and organ-specific inflammation. Efferent vagus nerve stimulation (VNS) should reverse this phenotype. Near-term fetal sheep (n=57) were surgically prepared with vascular catheters and ECG electrodes as control and treatment groups (lipopolysaccharide (LPS), Vx+LPS, Vx+LPS+selective efferent VNS). Fetal arterial blood samples were drawn for 7 days to profile inflammation (IL-6), insulin, blood gas and metabolism (glucose). At 54 h, a necropsy was performed; terminal ileum macrophages; CD11c (M1 phenotype) immunofluorescence was quantified to detect inflammation. Across the treatment groups, blood gas and cardiovascular changes indicated mild septicemia. At 3 h, in the LPS group IL-6 peaked; that peak was decreased in Vx+LPS400 and doubled in Vx+LPS800 group; the efferent VNS sped up the reduction of the inflammatory response profile over 54 h. M1 macrophage activity was increased in the LPS and Vx+LPS800 groups only. Glucose and insulin levels in the Vx+LPS group were respectively 1.3-fold and 2.3-fold higher vs. control at 3 h, and the efferent VNS normalized glucose levels. Complete withdrawal of vagal innervation results in a 72h delayed onset of sustained increase in glucose levels for at least 54h and intermittent hyperinsulinemia. Under conditions of moderate fetal inflammation, this is related to higher levels of gut inflammation; the efferent VNS reduces the systemic inflammatory response as well as restores both the levels of glucose and terminal ileum inflammation, but not the insulin levels. Our findings reveal a novel regulatory, hormetic, role of the vagus nerve in the immunometabolic response to endotoxin in near-term fetuses.
Code (0)
등록된 구현이 없습니다.
Similar Papers 제목 키워드 기반
The role of the vagus nerve during fetal development and its relationship with the environment
The autonomic nervous system (ANS) regulatory capacity begins before birth as the sympathetic and parasympathetic activity contributes significantly to the fetus' development. Several studies have shown how vagus nerve i…
Heart Rate VariabilityManagementVagus nerve manipulation and microglial plasticity in the prenatal brain
The efferent and afferent effects of the vagus nerve on the developing brain have remained enigmatic. Here we review the evidence of such effects on microglial plasticity in the sheep model of human fetal development, on…
Recording and manipulation of vagus nerve electrical activity in chronically instrumented unanesthetized near term fetal sheep
Background: The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli. This is due to the unique amenability of the unanesthetized fetal she…
The neonatal sepsis is diminished by cervical vagus nerve stimulation and tracked non-invasively by ECG: a preliminary report in the piglet model
An electrocardiogram (ECG)-derived heart rate variability (HRV) index reliably tracks the inflammatory response induced by low-dose lipopolysaccharide (LPS) in near-term sheep fetuses. We evaluated the effect of vagus ne…
Heart Rate VariabilityA novel statistical methodology for quantifying the spatial arrangements of axons in peripheral nerves
A thorough understanding of the neuroanatomy of peripheral nerves is required for a better insight into their function and the development of neuromodulation tools and strategies. In biophysical modeling, it is commonly …