Reinnervation of syngeneic pancreatico-duodenal grafts in rats.

Abstract

Knowledge on the reinnervation of transplanted organs is scarce, and the aim of the study was therefore to evaluate to what degree syngeneic pancreas grafts were reinnervated in rats. Syngeneic pancreatico-duodenal transplantations were performed in normoglycemic Wistar-Furth rats. Native and transplanted pancreas and duodenum were removed 4 or 40 weeks after implantation, and processed for indirect immunofluorescence using antibodies directed against vasoactive intestinal peptide, substance P (SP), calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), tyrosine hydroxylase (TH), or the general neuronal marker protein gene product 9.5. Four weeks after transplantation a moderate to rich number of protein gene product 9.5-positive nerve fibers were found homogeneously distributed through the pancreas, probably representing the intrapancreatic nervous system, because the grafted pancreas lacked both a sympathetic (TH/NPY) and sensory (SP/CGRP) innervation 4 weeks after implantation. In a few of the 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 seemed to emanate from intrapancreatic ganglia and possibly also from enteric neurons in adjacent parts of the duodenum. A few scattered vasoactive intestinal peptide-containing nerve fibers probably also emanating from local ganglia could be seen throughout the grafted pancreas both 4 and 40 weeks after transplantation. At 40 weeks after transplantation sympathetic (TH- and NPY-positive) nerve fibers were regularly seen, whereas CGRP-positive nerve 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 grafted pancreas of some rats 38 weeks after transplantation, i.e., 2 weeks before killing. True Blue-labeled nerve cell bodies were numerous in the celiac ganglion (presumably sympathetic nerves) and few in dorsal root ganglia (sensory nerves). The data suggest that the transplanted rat pancreas becomes reinnervated by mainly sympathetic nerve fibers.