vasoactive-intestinal-peptide and Enterocolitis--Necrotizing

Excessive inflammatory cell infiltration and accumulation in the intestinal mucosa are pathological features of necrotizing enterocolitis (NEC) leading to intestinal barrier disruption. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent that regulates intestinal epithelial barrier homeostasis. We previously demonstrated that VIP-ergic neuron expression is decreased in experimental NEC ileum, and this may be associated with inflammation and barrier compromise. We hypothesize that exogenous VIP administration has a beneficial effect in NEC.. NEC was induced in C57BL/6 mice by gavage feeding, hypoxia, and lipopolysaccharide administration between postnatal day (P) 5 and 9. There were four studied groups: Control (n = 6): Breast feeding without stress factors; Control + VIP (n = 5): Breast feeding + intraperitoneal VIP injection once a day from P5 to P9; NEC (n = 9): mice exposed to NEC induction; NEC + VIP (n = 9): NEC induction + intraperitoneal VIP injection. Terminal ileum was harvested on P9. NEC severity, intestinal inflammation, (IL-6 and TNFα), and Tight junctions (Claudin-3) were evaluated.. NEC severity and intestinal inflammation were significantly decreased in NEC + VIP compared to NEC. Tight junction expression was significantly increased in NEC + VIP compared to NEC.. VIP administration has a beneficial therapeutic effect in NEC by reducing inflammation and tight junction disruption.

Topics: Animals; Anti-Inflammatory Agents; Claudin-3; Disease Models, Animal; Enterocolitis, Necrotizing; Ileum; Interleukin-6; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Tight Junctions; Tumor Necrosis Factor-alpha; Vasoactive Intestinal Peptide

A mature enteric nervous system (ENS) is required to ensure a normal pattern of intestinal motility in order to regulate digestion after birth. We hypothesized that neuronal and glial components of the ENS would mature during the first postnatal days in preterm pigs that are a sensitive animal model of food intolerance and necrotizing enterocolitis (NEC). Stereological volume densities of the general neuronal population [assessed by betaIII-tubulin immunoreactivity (IR)] and subsets of neuronal (VIP-IR and nitrergic IR) and glial cells (GFAP-IR and S100-IR) were determined in the small intestine of newborn preterm piglets (93% gestation), after 3 days of receiving total parenteral nutrition (TPN) and after 3 days of TPN plus 2 days of enteral feeding with sow's colostrum or milk formula. Following TPN, VIP in the myenteric and inner submucous plexus and GFAP in the inner submucous plexus increased, while the relative volume of the total neuronal population remained constant. Introduction of enteral food induced variable degrees of food intolerance and NEC, especially after formula feeding, a diet that gave rise to a higher myenteric VIP and GFAP content in the inner submucous plexus than colostrum feeding. However, the ENS seemed unaffected by the presence of NEC-like intestinal lesions. Nevertheless, this study shows that the ENS is highly plastic during the first days after premature birth and adapts in an age- and diet-dependent manner. The observed postnatal adaptation in enteric VIP and GFAP may help to maintain intestinal homeostasis during suboptimal feeding regimens in preterm neonates.

Topics: Animals; Animals, Newborn; Diet; Enteric Nervous System; Enterocolitis, Necrotizing; Female; Intestines; Neuroglia; Neurons; Parenteral Nutrition, Total; Pregnancy; Premature Birth; Random Allocation; Swine; Vasoactive Intestinal Peptide