ENTERIC NERVOUS SYSTEM INJURY IN EXPERIMENTAL COLITIS

V Templeman, K Jacobson

Department of Pediatric Gastroenterology, British Columbia Children’s Hospital, Vancouver, British Columbia

In inflammatory bowel disease the enteric nervous system (ENS) is subject to repeated injury that may result in transient and permanent structural and functional alterations.

AIM: To evaluate the ENS response to intestinal inflammation by determining the extent of neuronal loss and whether neuronal apoptosis predominates in the myenteric plexus (MP) of the distal colon in a murine model of acute colitis.

METHODS: Colitis was induced in C3H/HEN female mice by intra-rectal administration of dinitrobenzene sulfonic acid (DNB, 6 mg in 100 ml 50% ethanol). Control mice received 50% ethanol. The inflammatory response was assessed by myeloperoxidase (MPO) activity. Neuronal loss and neuronal apoptosis were assessed using H & E sections and TUNEL method respectively. To eliminate underestimating the number of apoptosis cells, animals were sacrificed at 6hr, 12 hr, 24 hr, 48 hr and 5 days post induction of colitis.

RESULTS: Colitis was associated with a significant increase in MPO activity above control at 4 hr, 6 hr, 12 hr and 24 hr (9.5, 22.6, 15.9 and 13,4 fold increase respectively). By day 5, MPO activity had returned to control levels. The mean total number of cells in the MP ganglia decreased by 50% at 12 hr from 10.39 ± 3.33 to 5.207 ± 0.36 (P = 0.04), and remained reduced thereafter. Similarly at 12 hr a 52% reduction in mean number of nerve cell bodies was evident (7.05 ± 1.9 to 3.41 ± 0.3, P = 0.03), and remained reduced thereafter. Neuronal apoptosis was evident at 4hr (27% of nerve cell bodies, P = 0.03 vs control), peaked at 12 hr (52% of nerve cell bodies, P = 0.001 vs control, P = 0.03 vs DNB at 4 hr) and gradually declined to control levels by day 5 (11% nerve cell bodies).

CONCLUSION: These data demonstrate that distal acute colitis is associated with significant neuronal loss in the myenteric plexus that is largely due to inflammation induced neuronal apoptosis. Such morphologic changes likely lead to altered neuro-effector cell interaction and altered gut physiology.

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