Enhanced intestinal motor response to cholecystokinin in post-Nippostrongylus brasiliensis-infected rats: modulation by CCK receptors and the vagus nerve.

The jejunal inflammation induced in rats by the nematode Nippostrongylus brasiliensis is followed by intestinal neuroimmune alterations including mast cell hyperplasia and nerve remodelling. On the other hand, cholecystokinin (CCK) plays a pivotal role in the regulation of intestinal motility. The aim of this study was to determine whether the intestinal motor response to CCK is altered 30 days after infection by N. brasiliensis. Thus, CCK-8 (50 microg kg(-1) intraperitoneally) disrupted the pattern of jejunal migrating myoelectric complexes for a longer time in postinfected rats (95.5 +/- 3.5 min) than in controls (48.1 +/- 5.1 min). This enhanced jejunal response was also found after oral administration of the potent releaser of endogenous CCK, soybean trypsin inhibitor. In contrast, no alteration of the inhibition of colonic motility by CCK administration was observed. The increased responsiveness of jejunal motility to CCK persisted after mast cell stabilisation or depletion but was prevented by atropine, devazepide and L-365260 (CCK-A and CCK-B receptor antagonists, respectively) and vagotomy. These results indicate that neuroimmune alterations after N. brasiliensis infection lead to an increased intestinal motility response to CCK that involves a cholinergic mediation, a vagal pathway and alterations in intestinal CCK-A and CCK-B receptors.

Autonomic dysfunction in Chagas disease: lack of participation of the vagus nerve.

To evaluate the possible role of the vagus nerve in the development of the dysautonomia in Chagas disease, we examined 18 nerves from chagasic patients and 8 from non-chagasic patients, autopsied at the Department of Pathology, Ribeirão Preto School of Medicine, Brazil. Histological analysis showed mild inflammatory infiltrate composed predominantly of T lymphocytes, in epi-, peri- and endoneurium. No parasites were observed. Semithin sections showed swollen unmyelinated fibres, occasional thinly myelinated fibres, degenerated and atrophic axons, related to myelinated fibres. These findings were confirmed by electron microscopy, and in teased fibres. The changes were observed both in chagasic and in non-chagasic patients. Statistical analysis of the morphometric findings (myelinated fibre density, axonal and fibre diameters) failed to show significant differences between the 2 groups. The frequency of myelinated fibres of various diameters was also similar in the 2 groups. The morphological and morphometrical findings in chagasic patients are mild, non-specific, and could be related to the age of the patients, or with artefacts, since they have also been observed in non-chagasic patients. Retrograde changes due to the ganglionic lesions in the innervated organs cannot be completely ruled out. Our results do not allow us to implicate the vagus nerve in the dysautonomia in Chagas disease.

Qualitative and quantitative morphology of the vagus nerve in experimental Chagas' disease in rats: a light microscopy study.

Male Wistar rats were inoculated intraperitoneally with approximately 2 x 10(6) Trypanosoma cruzi Y strain blood forms. On days 7, 50, and 185 after inoculation, the animals were killed, and the right cervical vagus nerve was dissected, postfixed in 1% osmium tetroxide, and embedded in epoxy resin (Araldite). Semi-thin transverse sections were stained with 1% toluidine blue, examined by light microscopy, and photographed. An image analysis system was used to measure the area and diameter of each nerve and each fiber visible on the photomicrographs. Inoculated animals killed on days 7 and 185 after inoculation did not present morphologic or morphometric alterations of the vagus nerve. Inoculated animals killed on day 50 after inoculation presented several degrees of structural disorders in the myelin sheaths compared with control animals. The morphometric data demonstrated that the diameter of the myelinated fibers was generally increased in inoculated animals killed on day 50 after inoculation. These results suggest that experimental Chagas' disease in rats causes myelin damage and axonal swelling of the myelinated fibers of the vagus nerve, and that this injury to the vagus nerve may be important for a better understanding of the pathogenic mechanisms of the cardiac and digestive alterations caused by T. cruzi.