Neuronal activation in the nucleus of the solitary tract following jejunal lipopolysaccharide in the rat.
BACKGROUND
Inflammation during systemic lipopolysaccharide (LPS) seems to be modulated by the CNS via afferent and efferent vagal pathways. We hypothesized that similar to systemic inflammation, local LPS in the gut lumen may also activate central neurons and aimed to identify potential molecular mechanisms.


METHODS
Male Wistar rats were equipped with an exteriorized canula in the proximal jejunum. LPS or vehicle were administered into the jejunum (10 mg ml(-1)). For further study of molecular mechanisms, LPS or vehicle were administered systemically (1 mg kg(-1)). Brain stem activation was quantified by Fos-immunohistochemistry in the vagal nucleus of the solitary tract (NTS) and the Area postrema which is exposed to systemic circulation. Serum LPS concentrations were also determined.


RESULTS
Jejunal LPS exposure entailed 91+/-12 (n=7) Fos-positive neurons in the NTS compared to 39+/-9 in controls (n=6; p<0.01), while serum LPS concentrations and Fos-positive neurons in the Area postrema were not different. Systemic LPS triggered 150+/-25 (n=6) and vehicle 52+/-6 Fos-positive neurons (n=7; p<0.01). The Fos count after systemic LPS was reduced to 99+/-30 following pretreatment with the cyclooxygenase inhibitor Naproxen (10 mg kg(-1); p>0.05 versus vehicle controls) and increased to 242+/-66 following the iNOS-inhibitor Aminoguanidine (15 mg kg(-1); p<0.01). In the Area postrema, 97+/-17 (n=6) neurons were counted in animals pretreated with systemic LPS compared to 14+/-4 in controls (n=7, p<0.001).


CONCLUSIONS
Central neuronal activation following inflammation after systemic LPS is modulated by cyclooxygenase and NO pathways. Local exposure to bacterial LPS in the gut lumen activates the NTS which may set the stage for efferent vagal modulation of intestinal inflammation.
Gakis
G
G
Ludwig-Maximilian's University, Department of Surgery, Grosshadern, Munich, Germany.
Mueller
M H
MH
Hahn
J
J
Glatzle
J
J
Grundy
D
D
Kreis
M E
ME
D000818:Animals; D004333:Drug Administration Routes; D007583:Jejunum / Q000294:innervation; D008070:Lipopolysaccharides / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000166:cytology*
D008070:Lipopolysaccharides; D016761:Oncogene Proteins v-fos