Anatomy and Neuroscience - Theses

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    Structural damage to the enteric nervous system following ischemia / reperfusion injury
    Thacker, Michelle Anne ( 2012)
    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 in I/R and may be beneficial for future studies investigating neuroprotective strategies against intestinal I/R injury.