• Kaneko H, Tache Y and Kusugami K (2002). Importance of medullary thyrotropin-releasing hormone in brain-gut circuits regulating gastric integrity: preclinical studies. J Gastroenterol 37 Suppl 14:128-32. Summary: Cold restraint stress (CRS) induced vagal-dependent corpus mucosal erosions with hemorrhage in rats. Aggressive factors such as gastric acid, pepsin, and high-amplitude contractions have been reported to be responsible for inducing the formation of gastric lesions. Thyrotropin-releasing hormone (TRH) microinjected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus induced similar vagally mediated gastric injuries as CRS, and both were prevented by immunoneutralization with TRH antibody injected centrally. These findings indicated that TRH action in the DMN may contribute to CRS-induced gastric mucosal lesions. However, either exogenous or endogenous TRH at a subthreshold dose, which did not increase gastric acid secretion, alleviated gastric injury induced by intragastric administration of a strong irritant in rats. Previous studies have shown that the vagus participates in adaptive cytoprotection. Vagotomy or intracisternal injection of TRH-antibody completely abolished the protective effect of a mild irritant pretreatment in rats. The number of c-Fos protein-positive cells in the DMN increased in the process of adaptive cytoprotection. These results suggest that vagal afferent nerves activated by a topical gastric irritant influence DMN activity by releasing endogenous TRH, leading to protection against injury induced by a subsequent strong irritant. The dual vagally mediated action of TRH in the medulla to regulate the gastric mucosa's response to injury reflects the balance between the aggressive (acid, pepsin, motility) and protective (prostaglandin, calcitonin gene-related peptide, nitric oxide) factors recruited by the level of vagal activation. These data indicate a crucial role of medullary TRH and gastric vagal efferent and afferent circuits in the modulation of gastric integrity. Department of Internal Medicine, Division of General Medicine, Aichi Medical University School of Medicine, 21 Karimata, Yazako, Nagakute, Aichi-gun, Aichi 480-1195, Japan.