Regenerating vagal afferents reinnervate gastrointestinal tract smooth muscle of the rat

Peripheral projections of the vagus are known to regenerate after subdiaphr agmatic vagotomy, but neither the question of whether the regenerating axon s are motor or sensory nor the issue of whether the fibers reinnervate thei r original targets have been addressed. To determine whether vagal afferent s regenerate and whether they differentiate into normal terminal specializa tions in the reinnervated target organ, male Sprague-Dawley rats underwent complete subdiaphragmatic vagotomies and were injected 18 weeks later with 3 mu l of 4% wheat germ agglutinin-horseradish peroxidase (WGA-HRP) in the left nodose ganglion. To provide a comparison group, an unoperated group (c ontrols) was injected with WGA-HRP in the left nodose ganglion. The esophag us, the entire stomach, the first 8 cm of the duodenum, and the hilus of th e liver were prepared as wholemounts and processed with tetramethyl benzidi ne. Vagal afferents were found to have regenerated and reinnervated the eso phagus, stomach, duodenum, and liver. Bundles (two or more axons), individu al vagal axons, and terminals in the stomach were counted and mapped with a sampling grid. At 18 weeks postvagotomy, the reinnervated stomach and duod enum contained normal terminals as well as aberrant endings and growth cone profiles. The ingrowing axons reestablished ipsilateral and contralateral projections in the same proportions seen in controls, although the overall density of the different regenerating elements had reached only 7-39% of co ntrol values. These findings demonstrate that the gastrointestinal tract an d liver can undergo dramatic afferent reinnervation after vagotomy. The pre sence of differentiated endings at 18 weeks suggests that some afferent fun ction(s) may be restored, and the expression of growth cones suggests that additional regeneration may be ongoing. (C) 2000 Wiley-Liss, Inc.