Reinnervation of syngeneic pancreatico-duodenal grafts in rats

Background Knowledge on the reinnervation of transplanted organs is scarce, and the aim of the study was therefore to evaluate to what degree syngenei c pancreas grafts were reinnervated in rats. Methods. Syngeneic pancreatico-duodenal transplantations were performed in normoglycemic Wistar-Furth rats. Native and transplanted pancreas and duode num were removed 4 or 40 weeks after implantation, and processed for indire ct immunofluorescence using antibodies directed against vasoactive intestin al peptide, substance P (SP), calcitonin gene-related peptide (CGRP), neuro peptide Y (NPY), tyrosine hydroxylase (TH), or the general neuronal marker protein gene product 9.5. Results. Four weeks after transplantation a moderate to rich number of prot ein gene product 9.5-positive nerve fibers were found homogeneously distrib uted through the pancreas, probably representing the intrapancreatic nervou s system, because the grafted pancreas lacked both a sympathetic (TH/NPY) a nd sensory (SP/CGRP) innervation 4 weeks after implantation. In a few of th e animals there was a marked increase in SP-immunoreactive nerves (lacking CGRP), most conspicuous in the duodenal portion, both 4 and 40 weeks after transplantation probably secondary to a chronic pancreatitis, The fibers se emed to emanate from intrapancreatic ganglia and possibly also from enteric neurons in adjacent parts of the duodenum. A few scattered vasoactive inte stinal peptide-containing nerve fibers probably also emanating from local g anglia could be seen throughout the grafted pancreas both 4 and 40 weeks af ter transplantation. At 40 weeks after transplantation sympathetic (TH- and NPY-positive) nerve fibers were regularly seen, whereas CGRP-positive nerv e fibers were still virtually lacking in the pancreas. To trace the origin of the ingrowing nerve fibers, the tracer True Blue was injected into the g rafted pancreas of some rats 38 weeks after transplantation, i.e., 2 weeks before killing. True Blue-labeled nerve cell bodies were numerous in the ce liac ganglion (presumably sympathetic nerves) and few in dorsal root gangli a (sensory nerves). Conclusions. The data suggest that the transplanted rat pancreas becomes re innervated by mainly sympathetic nerve fibers.