Persistent epithelial barrier alterations in a rat model of postinfectious gut dysfunction

• Published in: Neurogastroenterology and motility 2011-11, Vol.23 (11), p.e523-e533
• Main Authors: Fernández‐Blanco, J. A., Barbosa, S., Sánchez de Medina, F., Martínez, V., Vergara, P.
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Capsaicin; Capsaicin - pharmacology; Chymases - metabolism; Digestive tract; Enteric nervous system; Enteric Nervous System - drug effects; Enteric Nervous System - pathology; Enteric Nervous System - physiopathology; epithelial barrier function; fluorescein; Gastrointestinal Tract - microbiology; Gastrointestinal Tract - pathology; Gastrointestinal Tract - physiopathology; Gastrointestinal tract diseases; Immunoglobulin E; Infection; Inflammation; Inflammation - etiology; Inflammation - pathology; Inflammation - physiopathology; Intestinal Mucosa - innervation; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Intestinal Mucosa - physiopathology; Intestine; Ion Transport - physiology; Male; mast cell; Mast cells; Mast Cells - cytology; Mast Cells - enzymology; Mast Cells - microbiology; Mast Cells - pathology; Mastocytosis; Mastocytosis - etiology; Mastocytosis - pathology; Mastocytosis - physiopathology; Membrane permeability; Mucosa; Neurons; Neurotransmitter Agents - pharmacology; Permeability; postinfectious gut dysfunction; Rats; Rats, Sprague-Dawley; Sensory System Agents - pharmacology; Serotonin; Sodium Channel Blockers - pharmacology; Substance P; Substance P - pharmacology; Tetrodotoxin; Tetrodotoxin - pharmacology; Trichinella spiralis; Trichinella spiralis - pathogenicity; Trichinellosis - complications; Trichinellosis - pathology; Trichinellosis - physiopathology
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/j.1365-2982.2011.01777.x

Background  Mucosal mast cells (MMCs), epithelial barrier function (EBF) and the enteric nervous system (ENS) are interactive factors in the pathophysiology of functional gastrointestinal disorders. We characterized postinfectious EBF alterations in the Trichinella spiralis infection model of MMC‐dependent intestinal dysfunction in rats. Methods  Sprague‐Dawley rats were infected with T. spiralis. 30 ± 2 days postinfection, jejunal EBF (electrophysiological parameters, fluorescein isothiocyanate‐dextran fluxes and responses to secretagogues and MMC degranulators) was evaluated (Ussing chamber). In some experiments, participation of secretomotor neurons was examined by tetrodotoxin (TTX) pretreatment. Jejunal histology and MMC count and activity were also assessed. Key Results  30 ± 2 days postinfection, when only a low grade inflammation was observed, increased MMC number and activity were associated with altered EBF. EBF alterations were characterized by increased mucosal permeability and ion secretion. In T. spiralis‐infected animals, secretory responses to serotonin (5‐HT) and immunoglobulin E (IgE)‐dependent activation of MMCs were reduced. In contrast, responses to substance P (SP) and capsaicin were similar in infected and noninfected animals. Neuronal blockade with TTX altered secretory responses to SP and capsaicin only in infected rats. Conclusions & Inferences  Trichinella spiralis infection in rats, at late stages, results in persistent postinfectious intestinal barrier dysfunctions and mucosal mastocytosis, with other signs suggestive of a low grade inflammation. The altered permeability and the TTX‐independent hyporesponsiveness to 5‐HT and IgE indicate epithelial alterations. Changes in responses to SP and capsaicin after neuronal blockade suggest an ENS remodeling during this phase. Similar long‐lasting neuro‐epithelial alterations might contribute to the pathophysiology of functional and postinfectious gastrointestinal disorders.