Regenerating vagal afferents reinnervate gastrointestinal tract smooth muscle of the rat

Abstract

Peripheral projections of the vagus are known to regenerate after subdiaphragmatic vagotomy, but neither the question of whether the regenerating axons are motor or sensory nor the issue of whether the fibers reinnervate their original targets have been addressed. To determine whether vagal afferents regenerate and whether they differentiate into normal terminal specializations in the reinnervated target organ, male Sprague‐Dawley rats underwent complete subdiaphragmatic vagotomies and were injected 18 weeks later with 3 μl of 4% wheat germ agglutinin‐horseradish peroxidase (WGA‐HRP) in the left nodose ganglion. To provide a comparison group, an unoperated group (controls) was injected with WGA‐HRP in the left nodose ganglion. The esophagus, the entire stomach, the first 8 cm of the duodenum, and the hilus of the liver were prepared as wholemounts and processed with tetramethyl benzidine. Vagal afferents were found to have regenerated and reinnervated the esophagus, stomach, duodenum, and liver. Bundles (two or more axons), individual vagal axons, and terminals in the stomach were counted and mapped with a sampling grid. At 18 weeks postvagotomy, the reinnervated stomach and duodenum 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 control values. These findings demonstrate that the gastrointestinal tract and liver can undergo dramatic afferent reinnervation after vagotomy. The presence of differentiated endings at 18 weeks suggests that some afferent function(s) may be restored, and the expression of growth cones suggests that additional regeneration may be ongoing. J. Comp. Neurol. 421:325–346, 2000. © 2000 Wiley‐Liss, Inc.

Regeneration of sensory but not motor axons following visceral nerve injury

“…This data parallels with vagal nerve transection studies that show sensory axons regenerate to restore connectivity to the gastrointestinal tract, while also re-establishing topographical organisation within organs (Phillips et al, 2000). However, as with the present study injured autonomic neurons consistently fail to reinnervate the gastrointestinal tract, lungs or heart (Phillips et al, 2003;Bregeon et al, 2007).…”

Gastrointestinal tract innervation of the mouse: afferent regeneration and meal patterning after vagotomy

“…One of the major objectives of the present experiments was to investigate whether the pattern of abdominal vagal regeneration previously observed for the rat (16,17) would generalize to the mouse and, thus, whether the mouse might be an advantageous preparation for examining the impact of particular growth factors and other gene products on vagal plasticity. A second major objective was to examine a set of ingestive end points that might serve as indexes of impairment and as measures of potential changes that might evolve over the course of an extended postsurgical interval.…”

“…In some animals, which served as sham controls, the laparotomy was immediately closed. The mice assigned to selective vagotomy groups received unilateral ventral trunk vagotomies designed to be similar to the selective vagotomy in the rat in similar experiments on vagal plasticity (16,17). Briefly, the ventral branch of the vagus nerve was isolated from the esophagus by blunt dissection, supported by a microdissecting hook, and cut with fine iris scissors above the point where the hepatic branch bifurcated from the main bundle.…”

“…When the animal sustains a unilateral truncal vagotomy above the highest abdominal branch (i.e., hepatic), afferents regenerate into the stomach and duodenal smooth muscle walls (16,17). These afferents continue to extend and ramify more and more distally within the stomach and duodenum over Ն45 wk after vagotomy.…”

Inhibitory effects on intake of cholecystokinin-8 and cholecystokinin-33 in rats with hepatic proper or common hepatic branch vagal innervation

“…Second, section of the gastroduodenal fibers probably provoked a regenerative response in the hepatic fibers (25,26). This could increase the response to CCK-33 in the liver by increasing the number of CCK-1 receptors on hepatic terminals or by increasing the efficiency of their transduction mechanisms.…”