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Ischemia reperfusion (I/R) injury can occur in a number of organs, however the intestine is possibly the most susceptible to I/R damage. Intestinal I/R injury is treated as a life threatening injury as tissue necrosis can rapidly progress and the non specific clinical presentation of the disease makes it difficult to diagnose. In addition, I/R injury is an inevitable consequence of intestinal transplantation and, with an increasing success rate, the demand for intestinal transplantation for end stage organ failure patients has increased. The damage caused to the intestine following a period of I/R has been well documented for a number of cell types, and results have demonstrated mucosal sloughing, muscle degeneration, and the damage caused to enteric neurons. However, the level of damage inflicted on enteric glia following I/R remains unexplored, despite the knowledge that glia contribute to neuronal maintenance and survival and are involved in maintaining mucosal integrity. Through the use of immunohistochemistry, this study shows for the first time that major damage to enteric glia occurs 3 hr following I/R injury, earlier than the peak of neuronal damage, and that structural damage to glia, revealed by cytoskeletal disruption (glial fibrillary acidic protein, GFAP, disaggregation) and loss of S100B, is associated with changes to the enteric neuronal protein, Hu in neighbouring neurons. I was able to quantify these changes, and to determine if the GFAP, S100B or Hu were differentially affected following arterial (A), venous (V), or arterial plus venous (AV) occlusion. In addition, through histochemistry, this study also documented the structural damage to the mucosa following A, V and AV occlusion. My study has added to our knowledge on the damaging effects of intestinal I/R injury on enteric glia, and has identified an association between the damage observed in enteric glia and neighbouring neurons. These results highlights the possible importance of enteric glia

During embryonic development of the peripheral nervous system (PNS), the adhesion molecule neuronal cadherin (N-cadherin) is expressed by Schwann cell precursors and associated with axonal growth cones. N-cadherin expression levels decrease as precursors differentiate into Schwann cells. In this study, we investigated the distribution of N-cadherin in the developing postnatal and adult rat peripheral nervous system. N-cadherin was found primarily in ensheathing glia throughout development, concentrated at neuron glial or glial glial contacts of the sciatic nerve, dorsal root ganglia (DRG), and myenteric plexi. In the sciatic nerve, N-cadherin decreases with age and progress of myelination. In adult animals, N-cadherin was found exclusively in nonmyelinating Schwann cells. The distribution of N-cadherin in developing E17 DRG primary cultures is similar to what was observed in vivo. Functional studies of N-cadherin in these cultures, using the antagonist peptide INPISGQ, show a disruption of the attachment between Schwann cells, but no interference in the initial or long-term contact between Schwann cells and axons. We suggest that N-cadherin acts primarily in the adhesion between glial cells during postnatal development. It may form adherents/junctions between nonmyelinating glia, which contribute to the stable tubular structure encapsulating thin caliber axons and thus stabilize the nerve structure as a whole.

Although there is pharmacological evidence to assume that the P2Y(4) receptor is a regulator of epithelial ion transport, no detailed data about its distribution within the gut are available. Therefore, this study, using whole mounts and cryosections, aimed to reveal the expression pattern of P2Y(4) along the entire guinea-pig gastrointestinal tract. P2Y(4) immunoreactivity was absent from enteric neurons but present in enteric glial cells of the stomach, small and large intestine. In the esophagus, P2Y(4) appeared to be exclusively located within striated muscle cells. P2Y(4) showed also a region dependency regarding its presence in different subpopulations of interstitial cells of Cajal: in myenteric interstitial cells of Cajal in the stomach and ileum; in some intramuscular interstitial cells in the stomach and cecum; in some deep muscular plexus interstitial cells in the ileum; and in some submucosal surface interstitial cells in the colon. These results and the knowledge that P2Y(4) activation causes intracellular Ca2+ recruitment led us to suggest that P2Y(4) in enteric glia plays a modulatory role in intercellular Ca2+ waves, while P2Y(4) in interstitial cells of Cajal modulates intracellular Ca2+ oscillations. (c) 2006 Elsevier B.V. All rights reserved.