TNF, VAGAL TONE AND GASTRIC MOTILITY

描述（改编自摘要）：校长的长期目标 研究者将解释对 消化功能与摄食行为变化的协调。 一 摄食行为与 消化包括抑制胃功能和相关的 恶心和不适，食欲不振，呕吐和腹泻是常见的 与传染病和恶性肿瘤相关的症状。 的 病理生理变化被认为是由释放的细胞因子介导的 宿主对抗原攻击的反应。 然而，具体的网站（S） 或这些尼古丁诱导的反应的作用机制尚不清楚。 肿瘤坏死因子-α（TNF-α）是最早被发现的细胞因子之一。 并在启动细胞因子级联反应中起关键作用 在宿主对挑战的反应中释放。 TNF被认为是主要的 脓毒症期间诱发的胃肠道（GI）症状的介质， 恶性肿瘤和其他与抑制 慢性传染病和恶性疾病的摄食行为。 最近的研究表明，背迷走神经复合体（DVC）是 缺乏血脑并且大的肽和蛋白质（例如， 激素、免疫球蛋白、补体、细胞因子）在循环中容易地 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。 的 已证实具有最高密度的可饱和TNF-α结合位点 在脑干里 因此，研究者假设TNF-α可能 代表了一种独特的化学“传入”信号， 迷走神经-迷走神经反射回路功能，从而抑制胃 在传染病和致癌疾病中发挥作用。 在拟议的实验中，研究人员重点关注急性 DVC内细胞因子TNF-α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， TNF-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，并为未来的研究奠定基础， 细胞因子作用于中枢回路的特定机制， 可能共同调节消化功能和摄食行为在慢性 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.