Efferent vagal nerve stimulation attenuates acute lung injury following burn: The importance of the gut-lung axis

Abstract

Background The purpose of this study was to assess acute lung injury when protection to the gut mucosal barrier offered by vagus nerve stimulation is eliminated by an abdominal vagotomy. Methods Male balb/c mice were subjected to 30% total body surface area steam burn with and without electrical stimulation to the right cervical vagus nerve. A cohort of animals were subjected to abdominal vagotomy. Lung histology, myeloperoxidase and ICAM-1 immune staining, myeloperoxidase enzymatic assay, and tissue KC levels were analyzed 24 hours after burn. Additionally, lung IkB-α, NF-kB immunoblots, and NF-kB-DNA binding measured by photon emission analysis using NF-kB-luc transgenic mice were performed. Results Six hours post burn, phosphorylation of both NF-kB p65 and IkB-α were observed. Increased photon emission signal was seen in the lungs of NF-kB-luc transgenic animals. Vagal nerve stimulation blunted NF-kB activation similar to sham animals whereas abdominal vagotomy eliminated the anti-inflammatory effect. After burn, MPO positive cells and ICAM-1 expression in the lung endothelium was increased, and lung histology demonstrated significant injury at 24 hours. Vagal nerve stimulation markedly decreased neutrophil infiltration as demonstrated by MPO immune staining and enzyme activity. Vagal stimulation also markedly attenuated acute lung injury at 24 hours. The protective effects of vagal nerve stimulation were reversed by performing an abdominal vagotomy. Conclusion Vagal nerve stimulation is an effective strategy to protect against acute lung injury following burn. Moreover, the protective effects of vagal nerve stimulation in the prevention of acute lung injury are eliminated by performing an abdominal vagotomy. These results establish the importance of the gut-lung axis after burn in the genesis of acute lung injury.

Enteric Glia Cells Attenuate Cytomix-Induced Intestinal Epithelial Barrier Breakdown

“…Breakdown of the gut barrier is associated with increases in systemic inflammation, distant organ injury, and death [4,6,7,14,20]. Studies have shown that modulation of intestinal epithelial tight junction proteins, through VNS, may be a potential strategy for attenuating gut barrier failure after injury [5,6,[13][14][15]. In this study, we explore the signaling pathway by which VNS maintains gut barrier integrity after injury, specifically focusing on the role of EGCs.…”

Electroacupuncture at Zusanli (ST36) Prevents Intestinal Barrier and Remote Organ Dysfunction following Gut Ischemia through Activating the Cholinergic Anti-Inflammatory-Dependent Mechanism

“…However, at present, there is still a lack of effective drugs or interventions to protect the gut epithelial barrier. Recent studies showed that electrical stimulation of the vagus nerve could protect intestinal barrier and alleviate inflammatory injury in intestine and remote organs of animals following burn injury by activation of the cholinergic anti-inflammatory pathway [5–8]. However, it is still difficult to apply electrical stimulation to the vagus nerve in clinical practice due to complicated manipulation and untoward side effects, including serious tissue injury.…”

CPSI-121 pharmacologically prevents intestinal barrier dysfunction after cutaneous burn through a vagus nerve-dependent mechanism

“…9 In this schema, when the neuroenteric axis is activated by VNS in a burn model, secondary acute lung injury is prevented. However, if abdominal vagotomy is performed, protective effects of VNS are eliminated and secondary acute lung injury occurs via the gut-lung axis.…”

“…However, if abdominal vagotomy is performed, protective effects of VNS are eliminated and secondary acute lung injury occurs via the gut-lung axis. 9 …”