Mechanisms mediating adult enteric neurogenesis are largely unknown. Using inflammation-associated neurogenesis models and a transgenic approach, we aimed to understand the cell-source for new neurons in infectious and inflammatory colitis. Dextran sodium sulfate (DSS) and Citrobacter rodentium colitis (CC) was induced in adult mice and colonic neurons were quantified. Sox2GFP and PLP1GFP mice confirmed the cell-type specificity of these markers. Sox2CreER:YFP and PLP1creER:tdT mice were used to determine the fate of these cells after colitis. Sox2 expression was investigated in colonic neurons of human patients with Clostridium difficile or ulcerative colitis. Both DSS and CC led to increased colonic neurons. Following colitis in adult Sox2CreER:YFP mice, YFP initially expressed predominantly by glia becomes expressed by neurons following colitis, without observable DNA replication. Similarly in PLP1CreER:tdT mice, PLP1 cells that co-express S100b but not RET also give rise to neurons following colitis. In human colitis, Sox2-expressing neurons increase from 1–2% to an average 14% in colitis. The new neurons predominantly express calretinin, thus appear to be excitatory. These results suggest that colitis promotes rapid enteric neurogenesis in adult mice and humans through differentiation of Sox2- and PLP1-expressing cells, which represent enteric glia and/or neural progenitors. Further defining neurogenesis will improve understanding and treatment of injury-associated intestinal motility/sensory disorders.
Myocardial bridging is recognized as an anatomical variation of the human coronary circulation in which an epicardial artery lies in the myocardium for part of its course. Thus, the vessel is 'bridged' by myocardium. The anterior interventricular branch of the left coronary artery has been reported as the most common site of myocardial bridges but other locations have been reported. The purpose of this study was to provide more definitive information on the vessels with myocardial bridges, the length and depth of the bridged segment, and the relationship between the presence of bridges and coronary dominance. Two hundred formalin-fixed human hearts were examined.Myocardial bridges were found in 69 (34.5%) of the hearts with a total of 81 bridges. One bridge was found in 59 of these hearts and multiple bridges were observed in ten (eight with double bridges and two with triple bridges).Bridges were most often found over the anterior interventricular artery (35 hearts). Bridges were also found over the diagonal branch of the left coronary artery (14), over the left marginal branch (five) and over the inferior interventricular branch of the left coronary artery (six). Bridges were also found over the right coronary artery (15 hearts), over the right marginal branch (four) and over the inferior interventricular branch of the right coronary artery (two). The presence of bridges appeared to be related to coronary dominance, especially in the left coronary circulation. Forty-six (66.6%) of the hearts with bridges were left dominant. Forty-two of these had bridges over the left coronary circulation and four over the right coronary circulation. Seventeen hearts (24.6%) were right dominant. Eleven of these had bridges over the right coronary circulation and six over the left coronary circulation.The remaining six hearts were co-dominant with four having bridges over the left coronary circulation and two over the right coronary circulation. The mean length of the bridges was 31 mm and the mean depth was 12 mm.The possible clinical implications of myocardial bridging may vary from protection against atherosclerosis to systolic vessel compression and resultant myocardial ischaemia.
These results show that colitis promotes enteric neurogenesis in the adult colon through a serotonin-dependent mechanism that drives glial cells to transdifferentiate into neurons.
In patients with LAMNs confined to the appendix, involvement of the appendectomy margin by neoplastic epithelium or acellular mucin does not predict recurrence of disease, even without further surgery. A conservative approach to managing these patients can be justified.
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