Neuroendocrine-bacterial interactions in a neurotoxin-induced model of trauma

The destruction of noradrenergic nerve cell innervation and resultant release of norepinephrine into the systemic circulation accompany severe tissue trauma. To examine whether destruction of noradrenergic neurons may directly influence the growth of indigenous bacteria in vivo, the selective noradrenergic neurotoxic agent 6-hydroxydopamine (6-OHDA) was employed in a murine model of trauma-induced norepinephrine release.

Following 6-OHDA administration, the cecums of 6- to 8-week-old male CF-1 mice were excised and examined for total bacterial counts and identification of bacterial species present in both the luminal space and intestinal wall. Lipopolysaccharide levels were also measured.

An increase of 3-5 logs in the total gram-negative population, most notably Escherichia coli, compared to controls on a per gram equivalent basis was observed at 1 day post-6-OHDA. Neurotoxin-induced alterations in cecal flora were completely 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 following 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 either the luminal contents or cecal tissue at any of the time points.

These results suggest that the destruction of noradrenergic neurons during trauma and consequent release of norepinephrine into the systemic circulation may influence the in vivo growth of the indigenous bacterial population within the gastrointestinal system.