Vagal nerve stimulation modulates gut injury and lung permeability in trauma-hemorrhagic shock

Abstract

BACKGROUND Hemorrhagic shock is known to disrupt the gut barrier leading to end-organ dysfunction. The vagus nerve can inhibit detrimental immune responses that contribute to organ damage in hemorrhagic shock. Therefore, we explored whether stimulation of the vagus nerve can protect the gut and recover lung permeability in trauma-hemorrhagic shock (THS). METHODS Male Sprague-Dawley rats were subjected to left cervical vagus nerve stimulation at 5 V for 10 minutes. The right internal jugular and femoral artery were cannulated for blood withdrawal and blood pressure monitoring, respectively. Animals were then subjected to hemorrhagic shock to a mean arterial pressure between 30 mm Hg and 35 mm Hg for 90 minutes then reperfused with their own whole blood. After observation for 3 hours, gut permeability was assessed with fluorescein dextran 4 in vivo injections in a ligated portion of distal ileum followed by Evans blue dye injection to assess lung permeability. Pulmonary myeloperoxidase levels were measured and compared. RESULTS Vagal nerve stimulation abrogated THS-induced lung injury (mean [SD], 8.46 [0.36] vs. 4.87 [0.78]; p < 0.05) and neutrophil sequestration (19.39 [1.01] vs. 12.83 [1.16]; p < 0.05). Likewise, THS gut permeability was reduced to sham levels. CONCLUSION Neuromodulation decreases injury in the THS model as evidenced by decreased gut permeability as well as decreased lung permeability and pulmonary neutrophil sequestration in a rat model.

Intestinal Epithelial TLR-4 Activation Is Required for the Development of Acute Lung Injury after Trauma/Hemorrhagic Shock via the Release of HMGB1 from the Gut

“…Of patients who survive their initial injury, a third develop remote organ injury(2), which may be reflective of immune dysregulation in response to the initial insult(3, 4). Of all the organs affected, injury to the lung is one of the leading causes of post-trauma morbidity(5), with an incidence of 79 per 100,000 persons/year, and carries a lethality of 40%(6),(7). Importantly, the mechanisms that mediate the induction of trauma-induced lung injury remain largely unexplained and represent a major gap in our knowledge in the field.…”

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

“…In addition to promoting an anti-inflammatory cholinergic response, VNS also directly improves the integrity of the tight gap junction proteins that regulate intestinal permeability 207 . VNS has also been shown to decrease intestinal permeability and improve the integrity of the blood-brain barrier, both of which would be beneficial following TBI 208,209 .…”

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

“…HMGB1 is a chromatin-associated protein that plays a key role in transcription and regulation of gene expression. It has also been implicated in the anti-inflammatory response observed in other studies of VNS ( 27 , 28 ). We also constrained our focus to the brainstem regions critical for cardio-respiratory control and implicated in neonatal morbidity and mortality ( 29 , 30 ).…”