Parasympathetic stimulation via the vagus nerve prevents systemic organ dysfunction by abrogating gut injury and lymph toxicity in trauma and shock
| Autor: | Da-Zhong Xu, Wei Dong, Vamsi Alli, Luis Ulloa, Gal Levy, Benjamin Chandler, Eleonora Feketova, Jordan E. Fishman, Edwin A. Deitch, Yong Qin |
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| Přispěvatelé: | Surgery, RS: NUTRIM - R2 - Gut-liver homeostasis |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Nervous system
Male medicine.medical_treatment Stimulation Pharmacology Receptors Nicotinic Critical Care and Intensive Care Medicine Neutrophil Activation Rats Sprague-Dawley ACTIVATION Mice Medicine Mesentery Shock Traumatic Cholecystokinin digestive oral and skin physiology Lung Injury Neuromodulation (medicine) Intestines medicine.anatomical_structure Anesthesia Emergency Medicine Lymph medicine.symptom Acetylcholine Vagus nerve stimulation medicine.drug Nicotine Vagus Nerve Stimulation Multiple Organ Failure Inflammation Lung injury Shock Hemorrhagic Article Permeability INFLAMMATION Parasympathetic Nervous System Animals business.industry Organ dysfunction medicine.disease Vagus nerve Rats Autonomic nervous system Intestinal Absorption RICH ENTERAL NUTRITION Cholinergic business Multiple organ dysfunction syndrome Spleen |
| Zdroj: | Shock, 39(5), 460-461. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 1073-2322 |
| Popis: | Trauma, hemorrhagic shock (T/HS), and subsequent multiple organ dysfunction syndrome (MODS) remain a current challenge in modern medicine. During trauma-hemorrhagic shock, intestinal injury and increased permeability leads to the generation of tissue injurious factors that are carried to the systemic circulation via the mesenteric lymphatics (1, 2). The gut has been shown to be a source of inflammatory factors with the capability of priming neutrophils and driving multiple organ failure after injury (3, 4), while gut protective strategies, involving both intraluminal and extraluminal modulators have demonstrated significant protection against the development of toxic post-shock mesenteric lymph and distant organ dysfunction (5–7). However, neural regulation via the vagus nerve, has been shown to be a critical component regulating normal intestinal function and intestinal defenses, the potentially protective effect of neuromodulation via stimulation of the vagus nerve on T/HS-induced gut injury and the production of biologically active mesenteric lymph has not been tested. While neural regulation of gut injury has not been extensively studied, the vagus nerve represents the longest parasympathetic nerve connecting the central nervous system with the principal visceral organs. The classical function of the vagus nerve is to control heart rate, hormone secretion, as well as digestion and peristalsis in the gastrointestinal tract. Furthermore, the vagus nerve allows bidirectional communication between the brain and the immune system as well as the organs it innervates. By activating the sensory fibers of the vagus nerve, the immune and organ systems can send signals to the brain that in turn stimulate the efferent fibers of the vagus nerve to control the peripheral immune system as well as organ function. For example, the effector neurons in the vagus nerve can inhibit the production of pro-inflammatory cytokines from tissue macrophages (8). Likewise, the vagus nerve is thought to be involved in maintenance of the intestinal mucosal barrier function as reflected in intrinsic neural and central neural modulation of host defense activity in infectious colitis and other inflammatory diseases (9, 10). In studies of endotoxemia, vagus nerve stimulation (VNS) was shown to decrease the systemic inflammatory response syndrome (SIRS) by attenuating the systemic inflammatory response to endotoxin (11). The pathway by which vagus nerve stimulation attenuates systemic inflammation after endotoxemia involved the spleen, because vagus nerve stimulation did not inhibits systemic inflammation in splenectomized mice (12). This pathway is termed the ‘cholinergic anti-inflammatory pathway’ because acetylcholine, the principle vagal neurotransmitter, inhibits the production of proinflammatory cytokines via the α7 nicotinic acetylcholine receptor subunit (α7nAChR) (8) as does nicotinic cholinergic agonists (13). Thus, from a clinical perspective, nicotine and other cholinergic agonists can potentially provide an alternative pharmacological strategy to mimic vagus nerve stimulation and to control systemic inflammation. Based on studies showing VNS is protective in burn injury (14) as well as endotoxemia and bacterial infective models (8, 11, 12), we hypothesize that neuromodulation via vagal stimulation would be protective in our trauma-hemorrhagic shock model. Specifically, we hypothesize that vagus nerve stimulation will prevent gut barrier injury after trauma and hemorrhagic shock and therefore decrease the production of toxic mesenteric lymph thereby protecting the lung from injury. We examine whether the spleen is a necessary organ conferring protection in the vagus nerve stimulation model and, finally, whether a nicotinic agonist can mimic the protective effects of the vagus nerve. |
| Databáze: | OpenAIRE |
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