TNF, VAGAL TONE AND GASTRIC MOTILITY

描述(摘自摘要)：校长的长期目标 研究人员将解释反应的生理机制 消化功能与进食行为的变化相协调。一个 进食行为与精神疾病关系的显著表现 消化涉及到胃功能的抑制和相关的 恶心和不适，食欲不振，呕吐和腹泻，这些都很常见 与感染性疾病和恶性肿瘤相关的症状。这个 病理生理变化被认为是由释放的细胞因子介导的。 由宿主对抗原的挑战作出反应。然而，具体的地点(S) 或者，这些细胞因子诱导的反应的作用机制尚不清楚。 肿瘤坏死因子-α是最早发现的细胞因子之一。 释放并在启动细胞因子级联反应中起关键作用 在主持人的回应中释放挑战。肿瘤坏死因子被认为是主要的 败血症期间引起的胃肠道(GI)症状的介体， 恶性，以及其他与抑制 慢性传染病和恶性疾病的摄食行为。 最近的研究表明，背侧迷走神经复合体(DVC)是 没有血脑并且大肽和蛋白质(例如， 激素、免疫球蛋白、补体、细胞因子)很容易在循环中 穿过这个区域的细胞外空间。DVC包含 大脑最终控制消化功能的回路。这个 已经证实了最高密度的可饱和的肿瘤坏死因子-α结合部位 在脑干里。因此，调查人员假设，肿瘤坏死因子-α可能 代表一种独特的化学“传入”信号，它可以直接改变 迷走神经-迷走神经反射回路功能，导致胃部抑制 在传染病和致癌性疾病中发挥作用。 在拟议的实验中，调查人员将重点放在急性 细胞因子肿瘤坏死因子α在DVC中的作用机制。从这些 神经生理学研究，他和他的同事将提供信息 肿瘤坏死因子-α如何通过作用于迷走神经回路来控制消化功能 在脑干内，并为未来研究 细胞因子在中枢环路中作用的特定机制 可能参与调节慢性胃炎患者的消化功能和进食行为 疾病。

DESCRIPTION (Adapted from the Abstract): A long-term goal of the Principal Investigator is to explain the physiological mechanisms responsive for the coordination of digestive functions with changes in ingestive behavior. A significant manifestation of the relation between ingestive behavior and digestion involves the suppression of gastric functions and the associated nausea and malaise, lost of appetite, vomiting, and diarrhea that are common symptoms associated with infectious illness and malignancy. The pathophysiological changes are though to be mediated by cytokines liberated by the host in response to antigenic challenge. Yet, the specific site(s) or mechanisms of action of these cytokine-induced responses are not clear. Tumor necrosis factor-alpha (TNF-alpha) is one of the first cytokines to be released and plays a pivotal role in initiating the cascade of cytokine release in the host response of challenge. TNF is thought to be the primary mediator of the gastrointestinal (GI) symptoms evoked during sepsis, malignancy, and other disease processes associated with the suppression of feeding behavior in chronic infectious and malignant disease. Recent studies have demonstrated that the dorsal vagal complex (DVC) is devoid of a blood-brain and that large peptides and proteins (e.g., hormones, immunoglobulin, complement, cytokines) in the circulation readily traverse the extracellular spaces of this area. The DVC contains the circuit through which the brain ultimately controls digestive function. The highest density of saturable, TNF-alpha binding sites has been demonstrated in the brainstem. Thus, the Investigator hypothesizes that TNF-alpha may represent a unique chemical "afferent" signal which directly alters vago-vagal reflex circuit function, resulting in a suppression of gastric functions during infectious and carcinogenic disease. In the proposed experiments, the Investigator focuses on the acute mechanisms of action of the cytokine TNF-alpha within the DVC. From these neurophysiological studies, he and his associates will provide information on how TNF-alpha can control digestive functions by acting on vagal circuits within the brainstem, and a foundation for future studies examining the specific mechanisms of actions of cytokines on the central circuits which may co-regulate digestive functions and ingestive behavior during chronic disease.