Vagal Afferent Fibers Contribute to the Anti-Inflammatory Reactions by Vagus Nerve Stimulation in Concanavalin A Model of Hepatitis in Rats

Abstract

Background: Increasing number of studies provide evidence that the vagus nerve stimulation (VNS) dampens inflammation in peripheral visceral organs. However, the effects of afferent fibers of the vagus nerve (AFVN) on anti-inflammation have not been clearly defined. Here, we investigate whether AFVN are involved in VNS-mediated regulation of hepatic production of proinflammatory cytokines. Methods: An animal model of hepatitis was generated by intraperitoneal injection of concanavalin A (ConA) into rats, and electrical stimulation was given to the hepatic branch of the vagus nerve. AFVN was selectively eliminated by treating animals with capsaicin (CAP). mRNA and protein expression in target tissues was analyzed by RT-PCR, real-time PCR, western blotting and immunofluorescence staining.Results: TNF-α, IL-1β, and IL-6 mRNAs and proteins that were induced by ConA in the liver macrophages were significantly reduced by the electrical stimulation of the hepatic branch of the vagus nerve (hVNS). hVNS also induced an increase in phospho-STAT3 in the liver macrophages of ConA-injected animals, suggesting the activation of STAT3 transcription factor associated with cholinergic anti-inflammation. Capsaicin (CAP) treatment deteriorated transient receptor potential vanilloid 1 (TRPV1)-positive neurons and also induced an increase in apoptotic caspase-3 signals in nodose ganglion (NG) neurons. Concomitantly, CAP suppressed choline acetyltransferase (ChAT) expression that was induced by hVNS in DMV neurons of ConA-injected animals. Furthermore, hVNS-mediated downregulation of TNF-α, IL-1β, and IL-6 expression was reduced by CAP administration. Conclusions: Our data indicate that the activity of AFVN contributes to hepatic anti-inflammatory responses mediated by hVNS in ConA model of hepatitis in rats.

Effects and neuroprotective mechanisms of vagus nerve stimulation on cognitive impairment with traumatic brain injury in animal studies: A systematic review and meta-analysis

“…As shown above, both VNS can reduce brain tissue or serum TNF-α levels by stimulating the left or right vagus nerve for 10-20 min in animals with weight-drop brain injury. It is not completely clear how VNS inhibits neuroinflammation and reduces inflammatory factors, such as TNF-α, but studies have found that VNS can activate alpha7 nicotinic acetylcholine receptor (α7nAChR) on microglia to regulate NF-κB, JAK2/STAT3, PI3K/AKT signaling pathways to inhibit the expression of TNF-α, IL-1, IL-6, and other inflammatory factors (33,43,44). In addition, Vishal Bansal et al found that VNS can upregulate the expression of brain gut peptides, which can reduce the release of TNF (30).…”