NEUROENDOCRINE-BACTERIAL INTERACTIONS IN A NEUROTOXIN-INDUCED MODEL OF TRAUMA

Background: The destruction of noradrenergic nerve cell innervation an d resultant release of norepinephrine into the systemic circulation ac company severe tissue trauma. To examine whether destruction of noradr energic neurons may directly influence the growth of indigenous bacter ia in vivo, the selective noradrenergic neurotoxic agent 6-hydroxydopa mine (6-OHDA) was employed in a murine model of trauma-induced norepin ephrine release. Materials and methods: Following 6-OHDA administratio n, the cecums of 6- to 8-week-old male CF-1 mice were excised and exam ined for total bacterial counts and identification of bacterial specie s present in both the luminal space and intestinal wall. Lipopolysacch aride levels were also measured. Results: An increase of 3-5 logs in t he total gram-negative population, most notably Escherichia coli, comp ared to controls on a per gram equivalent basis was observed at 1 day post-6-OHDA. Neurotoxin-induced alterations in cecal flora were comple tely inhibited by the prior administration of the catecholamine uptake blocker desipramine hydrochloride, indicating the specificity of the effect being due to the released norepinephrine. Within 14 days follow ing chemical sympathectomy, during which regeneration of noradrenergic neurons occurs, the cecal flora returned to the distribution observed in controls. Levels of lipopolysaccharide were not increased in eithe r the luminal contents or cecal tissue at any of the time points. Conc lusions: These results suggest that the destruction of noradrenergic n eurons during trauma and consequent release of norepinephrine into the systemic circulation may influence the in vivo growth of the indigeno us bacterial population within the gastrointestinal system. (C) 1997 A cademic Press.