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Background Gut barrier failure has been implicated in the progression from single organ injury to multiple organ failure. The unstirred mucus layer is a major component of the physiological gut barrier, its role in acute pancreatitis(AP) is not clearly defined. Study Design Rats underwent biliopancreatic duct ligation-induced AP; two controls were used: biliopancreatic duct ligation with drainage and sham duct ligation. After 4.5 hours, serum and ascitic amylase activity was measured. Mucus was analyzed for reactive nitrogen intermediates(RNI)-mediated damage, reactive oxygen species(ROS)-induced damage, and total antioxidant capacity. Mucus coverage and villous injury was assessed histologically. Ileum permeability was measured by diffusion of a fluorescent dextran probe. Histology and morphology of the mucus layer were validated in a mouse AP model (intraductal taurocholate plus caerulein). Results Biliopancreatic duct ligation increased serum α-amylase, ascitic volume, and ascitic α-amylase. Intestinal permeability was increased, which was associated with loss of the unstirred mucus layer but not villous injury. These changes correlated with increased ROS-and-RNI-mediated mucus damage as well as decreased mucus total antioxidant capacity but were not present in the two control groups. Using a different model of AP in mice, the finding of mucus layer disruption was recapitulated at 6 hours after AP, but by 24 hours, rebound hypersecretion of inspissated mucus was seen. Conclusions These results support the hypothesis that damage to the unstirred mucus layer with evidence of oxidative stress occurs during AP-induced gut barrier failure.

Pediatric traumatic brain injury (TBI) is a significant and underappreciated societal problem. Whereas many TBI studies have evaluated the mechanisms of cell death after TBI, fewer studies have evaluated the extent to which regeneration is occurring. Here we used a cryoinjury model to damage the somatosensory cortex of rats at postnatal day 6 (P6), P10 and P21. We evaluated the production of new neocortical neurons using a combination of 5-bromo-2-deoxyuridine (BrdU) labeling combined with staining for doublecortin (DCX). BrdU+/DCX+ bipolar cells were observed adjacent to the neocortical lesion, with their processes oriented perpendicular to the pial surface. As the animals aged, both the overall proliferative response as well as the production of neocortical neuroblasts diminished, with P6 animals responding most robustly, P10 animals less strongly, and P21 animals showing a very modest proliferative response and virtually no evidence of neocortical neurogenesis. When BrdU was administered at increasingly delayed intervals after the injury at P6, there was a clear difference in the number of new neuroblasts produced as a function of age, with the greatest number of new neocortical neurons produced between 4 and 7 days after the injury. These studies demonstrate that the immature brain has the capacity to produce neocortical neurons after traumatic injury, but this capacity diminishes as the brain continues to develop. Furthermore, in contrast to moderate hypoxic/ischemic brain damage in the P6 rat, where neurogenesis persists for at least 2 months, the response to cryoinjury is quite different as the neurogenic response diminishes over time.

Structured Abstract Objective To test whether the mucus layer, luminal digestive enzymes, and intestinal mast cells are critical components in the pathogenesis of trauma-shock-induced gut and lung injury. Summary Background Data Gut-origin sepsis studies have highlighted the importance of the systemic component (ischemia-repefusion) of gut injury while the intraluminal component is less well studied. Methods In rats subjected to trauma-hemorrhagic shock (T/HS) or sham-shock (T/SS), the role of pancreatic enzymes in gut injury was tested by diversion of pancreatic enzymes via pancreatic duct exteriorization (PDE), while the role of the mucus layer was tested via the enteral administration of a mucus surrogate. Additionally the role of mast cells was assessed by measuring mast cell activation and the ability of pharmacologic inhibition of mast cells to abrogate gut and lung injury. Gut and mucus injury was characterized functionally, morphologically and chemically. Results PDE abrogated T/HS-induced gut barrier loss and limited chemical mucus changes. The mucus surrogate prevented both T/HS-induced gut and lung injury. Lastly, pancreatic enzyme-induced gut and lung injury appears to involve mast cell activation, since T/HS activates mast cells and pharmacologic inhibition of intestinal mast cells prevented T/HS-induced gut and lung injury. Conclusions These results indicate that gut and gut-induced lung injury after T/HS involves a complex process consisting of intraluminal digestive enzymes, the unstirred mucus layer, and a systemic ischemic-reperfusion injury. This suggests the possibility of intraluminal therapeutic strategies.