TNF plays a pathogenic role in inflammatory bowel diseases (IBDs), which are characterized by altered cytokine production and increased intestinal epithelial cell apoptosis. In vitro studies suggest that kinase suppressor of Ras-1 (KSR1) is an essential regulatory kinase for TNF-stimulated survival pathways in intestinal epithelial cell lines. Here we use a KSR1-deficient mouse model to study the role of KSR1 in regulating intestinal cell fate during cytokine-mediated inflammation. We show that KSR1 and its target signaling pathways are activated in inflamed colon mucosa. Loss of KSR1 increases susceptibility to chronic colitis and TNF-induced apoptosis in the intestinal epithelial cell. Furthermore, disruption of KSR1 expression enhances TNF-induced apoptosis in mouse colon epithelial cells and is associated with a failure to activate antiapoptotic signals including Raf-1/MEK/ERK, NF-kappaB, and Akt/protein kinase B. These effects are reversed by WT, but not kinase-inactive, KSR1. We conclude that KSR1 has an essential protective role in the intestinal epithelial cell during inflammation through activation of cell survival pathways.

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Vein grafts have been used both experimentally and clinically to bridge gaps in peripheral nerves. This study describes a modification of the vein graft technique in which vein graft conduits are pulled inside-out before anastomosis with proximal and distal nerve stumps. This technique creates an autogenous vein conduit with the collagen-rich adventitial surface exposed to the regenerating axons. The inside-out technique is a fast and simple modification of the standard vein graft technique and produces an accelerated rate of nerve regeneration and significantly earlier myelination compared with the results obtained from the use of polyethylene nerve guides and standard vein graft conduits.

The use of non-neural conduits to bridge gaps in peripheral nerves has been noted in the literature for many years. A logical extension of this concept is the introduction of neurotrophic or growth promoting factors into the lumen. We present here an injectable nerve guide that allows percutaneous access to the microenvironment of the regenerating peripheral nerve within the guide's lumen. Hyaluronic acid, a compound associated with decreased scarring and improved fibrin matrix formation, is added sequentially to the regenerating peripheral rat sciatic nerve via this injectable nerve guide. Assessment of nerve regeneration and reinnervation shows better conduction velocity, higher axon counts, and a trend toward earlier myelination with hyaluronic acid compared with saline. This work not only implies hyaluronic acid's role as an agent that aids nerve growth but also describes a new tool that allows percutaneous access to the milieu of a regenerating nerve.

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